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Inhibition of CDK7 mitigates doxorubicin cardiotoxicity and enhances anticancer efficacy Cardiovasc. Res. (IF 10.8) Pub Date : 2024-04-22 Jingrui Chen, Jing Wei, Peng Xia, Yuening Liu, Mahder Dawit Belew, Ryan Toohill, Boyang Jason Wu, Zhaokang Cheng
Aims The anthracycline family of anticancer agents such as doxorubicin (DOX) can induce apoptotic death of cardiomyocytes and cause cardiotoxicity. We previously reported that DOX-induced apoptosis is accompanied by cardiomyocyte cell cycle-reentry. Cell cycle progression requires cyclin-dependent kinase 7 (CDK7)-mediated activation of downstream cell cycle CDKs. This study aims to determine whether
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Mechanisms of ischaemia-induced arrhythmias in hypertrophic cardiomyopathy: a large-scale computational study Cardiovasc. Res. (IF 10.8) Pub Date : 2024-04-22 James A Coleman, Ruben Doste, Zakariye Ashkir, Raffaele Coppini, Rafael Sachetto, Hugh Watkins, Betty Raman, Alfonso Bueno-Orovio
Aims Lethal arrhythmias in hypertrophic cardiomyopathy (HCM) are widely attributed to myocardial ischaemia and fibrosis. How these factors modulate arrhythmic risk remains largely unknown, especially as invasive mapping protocols are not routinely used in these patients. By leveraging multiscale digital-twin technologies, we aim to investigate ischaemic mechanisms of increased arrhythmic risk in HCM
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Aquaporins enriched in endothelial vacuole membrane regulate the diameters of microvasculature in hyperglycemia Cardiovasc. Res. (IF 10.8) Pub Date : 2024-04-22 Changsheng Chen, Yinyin Qin, Yidan Xu, Xiaoning Wang, Wei Lei, Xiaozhong Shen, Lixun Chen, Linnong Wang, Jie Gong, Yongming Wang, Shijun Hu, Dong Liu
Background In patients with diabetic microvascular complications, decreased perfusion or vascular occlusion, caused by reduced vascular diameter, is a common characteristic that will lead to insufficient blood supply. Yet, the regulatory mechanism and effective treatment approach remain elusive. Methods and Results Our initial findings revealed a notable decrease in the expression of human AQP1 in
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NLRP3 inflammasome-mediated premature immunosenescence drives diabetic vascular aging dependent on the induction of perivascular adipose tissue dysfunction Cardiovasc. Res. (IF 10.8) Pub Date : 2024-04-21 Guang-Jie Tai, Yan-Jie Ma, Jun-Lin Feng, Jia-Peng Li, Shu Qiu, Qing-Qing Yu, Ren-Hua Liu, Silumbwe Ceaser Wankumbu, Xin Wang, Xiao-Xue Li, Ming Xu
Aims The vascular aging process accelerated by type 2 diabetes mellitus (T2DM) is responsible for the elevated risk of associated cardiovascular diseases (CVDs). Metabolic disorder-induced immune senescence has been implicated in multi-organ/tissue damage. Herein, we sought to determine the role of immunosenescence in diabetic vascular aging and to investigate the underlying mechanisms. Methods and
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New insight into air pollution-related cardiovascular disease: an adverse outcome pathway framework of PM2.5-associated vascular calcification Cardiovasc. Res. (IF 10.8) Pub Date : 2024-04-18 Ruiyang Ding, Linyuan Huang, Kanglin Yan, Zhiwei Sun, Junchao Duan
Despite the air quality has been generally improved in recent years, ambient fine particulate matter (PM2.5), a major contributor to air pollution, remains one of the major threats to public health. Vascular calcification is a systematic pathology associated with an increased risk of cardiovascular disease. Although the epidemiological evidence has uncovered the association between PM2.5 exposure and
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Isthmin-1 alleviates cardiac ischemia/reperfusion injury through cGMP-PKG signaling pathway Cardiovasc. Res. (IF 10.8) Pub Date : 2024-04-18 Min Hu, Xin Zhang, Can Hu, Zhen-Guo Ma, Sha-Sha Wang, Teng Teng, Xiao-Feng Zeng, Qi-Zhu Tang
Aims Ischemia/reperfusion (I/R) injury is an important complication of reperfusion therapy for acute myocardial infarction, extremely compromising the cardiac benefits of revascularization, however, specific and efficient treatment for cardiac I/R injury is still lacking. Isthmin-1 (ISM1) is a novel adipokine, and plays indispensable roles in regulating glycolipid metabolism and cell survival. The
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The proprotein convertase FURIN is a novel aneurysm predisposition gene impairing TGF-β signaling Cardiovasc. Res. (IF 10.8) Pub Date : 2024-04-18 Zongsheng He, Arne S IJpma, Dianne Vreeken, Daphne Heijsman, Karen Rosier, Hence J M Verhagen, Jorg de Bruin, Hennie T Brüggenwirth, Jolien W Roos-Hesselink, Jos A Bekkers, Danny Huylebroeck, Heleen van Beusekom, John W M Creemers, Danielle Majoor-Krakauer
Aim Aortic aneurysms (AA) frequently involve dysregulation of transforming growth factor β (TGF-β)-signaling in the aorta. Here, FURIN was tested as aneurysm predisposition gene given its role as proprotein convertase in pro-TGF-β maturation. Methods and results Rare FURIN variants were detected by whole-exome sequencing of 781 unrelated aortic aneurysm patients and affected relatives. Thirteen rare
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Ncf1 knockout in SMCs exacerbates angiotensin II-induced aortic aneurysm and dissection by activating the STING pathway Cardiovasc. Res. (IF 10.8) Pub Date : 2024-04-17 Hao Liu, Peiwen Yang, Shu Chen, Shilin Wang, Lang Jiang, Xiaoyue Xiao, Sheng Le, Shanshan Chen, Xinzhong Chen, Ping Ye, Jiahong Xia
Aims Aortic aneurysm and dissection (AAD) is caused by the progressive loss of aortic smooth muscle cells (SMCs) and is associated with a high mortality rate. Identifying the mechanisms underlying SMC apoptosis is crucial for preventing AAD. Neutrophil cytoplasmic factor 1 (Ncf1) is essential in reactive oxygen species (ROS) production and SMC apoptosis; Ncf1 absence leads to autoimmune diseases and
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Mast cells: a novel therapeutic avenue for cardiovascular diseases? Cardiovasc. Res. (IF 10.8) Pub Date : 2024-04-17 Remo Poto, Gianni Marone, Stephen J Galli, Gilda Varricchi
Mast cells are tissue-resident immune cells strategically located in different compartments of the normal human heart (the myocardium, pericardium, aortic valve and close to nerves) as well as in atherosclerotic plaques. Cardiac mast cells produce a broad spectrum of vasoactive and proinflammatory mediators, which have potential roles in inflammation, angiogenesis, lymphangiogenesis, tissue remodeling
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Endothelial NLRP3 inflammasome regulation in atherosclerosis Cardiovasc. Res. (IF 10.8) Pub Date : 2024-04-16 Shuai Guo, Litao Wang, Kaixiang Cao, Ziling Li, Mingchuan Song, Shuqi Huang, Zou Li, Cailing Wang, Peiling Chen, Yong Wang, Xiaoyan Dai, Xianglin Chen, Xiaodong Fu, Du Feng, Jun He, Yuqing Huo, Yiming Xu
Aim The activation of Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in endothelial cells (ECs) contributes to vascular inflammation in atherosclerosis. Considering the high glycolytic rate of ECs, we delineated whether and how glycolysis determines endothelial NLRP3 inflammasome activation in atherosclerosis. Methods and Results Our results demonstrated a significant
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ATP13A3 variants promote pulmonary arterial hypertension by disrupting polyamine transport Cardiovasc. Res. (IF 10.8) Pub Date : 2024-04-16 Bin Liu, Mujahid Azfar, Ekaterina Legchenko, James A West, Shaun Martin, Chris Van den Haute, Veerle Baekelandt, John Wharton, Luke Howard, Martin R Wilkins, Peter Vangheluwe, Nicholas W Morrell, Paul D Upton
Aims Potential loss-of-function variants of ATP13A3, the gene encoding a P5B-type transport ATPase of undefined function, were recently identified in pulmonary arterial hypertension (PAH) patients. ATP13A3 is implicated in polyamine transport but its function has not been fully elucidated. Here, we sought to determine the biological function of ATP13A3 in vascular endothelial cells and how PAH-associated
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Blood-based cardiometabolic phenotypes in atrial fibrillation and their associated risk: EAST-AFNET 4 biomolecule study Cardiovasc. Res. (IF 10.8) Pub Date : 2024-04-13 Larissa Fabritz, Winnie Chua, Victor R Cardoso, Christoph Al-Taie, Katrin Borof, Anna Suling, Linda Krause, Shino Kany, Christina Magnussen, Karl Wegscheider, Guenter Breithardt, Harry J G M Crijns, A John Camm, George Gkoutos, Patrick T Ellinor, Andreas Goette, Ulrich Schotten, Ursula-Henrike Wienhues-Thelen, Tanja Zeller, Renate B Schnabel, Antonia Zapf, Paulus Kirchhof
Background Atrial fibrillation (AF) and concomitant cardiometabolic disease processes interact and combine to lead to adverse events such as stroke, heart failure, myocardial infarction, and cardiovascular death. Circulating biomolecules provide quantifiable proxies for cardiometabolic disease processes. Their role in defining subphenotypes of AF is not known. Methods and results This prespecified
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DNA double-stranded breaks, a hallmark of aging, defined at the nucleotide resolution, are increased and associated with transcription in the cardiac myocytes in LMNA-cardiomyopathy Cardiovasc. Res. (IF 10.8) Pub Date : 2024-04-05 Benjamin Cathcart, Sirisha M Cheedipudi, Leila Rouhi, Zhongming Zhao, Priyatansh Gurha, Ali J Marian
Aims An intrinsic feature of gene transcription is the formation of DNA superhelices near the transcription bubble, which are resolved upon induction of transient double-stranded breaks (DSBs) by topoisomerases. Unrepaired DSBs are pathogenic as they lead to cell cycle arrest, senescence, inflammation, and organ dysfunction. We posit that DSBs would be more prevalent at the genomic sites that are associated
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Interleukin-1 receptor accessory protein blockade limits the development of atherosclerosis and reduces plaque inflammation Cardiovasc. Res. (IF 10.8) Pub Date : 2024-04-02 Megan Mulholland, Marie A C Depuydt, Gabriel Jakobsson, Irena Ljungcrantz, Andrietta Grentzmann, Fong To, Eva Bengtsson, Elin Jaensson Gyllenbäck, Caitríona Grönberg, Sara Rattik, David Liberg, Alexandru Schiopu, Harry Björkbacka, Johan Kuiper, Ilze Bot, Bram Slütter, Daniel Engelbertsen
Aims The interleukin-1 receptor accessory protein (IL1RAP) is a co-receptor required for signalling through the IL-1, IL-33, and IL-36 receptors. Using a novel anti-IL1RAP-blocking antibody, we investigated the role of IL1RAP in atherosclerosis. Methods and results Single-cell RNA sequencing data from human atherosclerotic plaques revealed the expression of IL1RAP and several IL1RAP-related cytokines
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A low bleeding risk thrombolytic agent: citPA5 Cardiovasc. Res. (IF 10.8) Pub Date : 2024-03-27 Shanli Chen, Sudan Fang, Yang Zhou, Zhiwei Huang, Shujuan Yu, Dan Chen, Zhiyou Wang, Yanyan Xu, Peiwen Liu, Yongkun Li, Wei Lin, Longguang Jiang, Cai Yuan, Mingdong Huang
Aims Alteplase is a cornerstone thrombolytic agent in clinical practice, but presents a potential bleeding risk. Stroke patients need pre-screening to exclude hemorrhagic stroke before using Alteplase. In this study, we develop a new thrombolytic agent citPA5, characterized by an enhanced safety profile and minimal bleeding tendency. Methods and results A clot lysis agent, named citPA5, is developed
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Lactiplantibacillus plantarum strains KABP011, KABP012 and KABP013 modulate bile acids and cholesterol metabolism in humans Cardiovasc. Res. (IF 10.8) Pub Date : 2024-03-25 T Padro, V de Santisteban, P Huedo, M Puntes, M Aguiló, J Espadaler-Mazo, L Badimon
Aims Probiotics with high bile salt hydrolase (BSH) activity have shown to promote cardiovascular health. However, their mechanism(s) of action remain poorly understood. Here, we performed a pilot exploratory study to investigate effects of a 4-week intervention with escalating doses of a BSH-active formula containing Lactiplantibacillus plantarum strains KABP011, KABP012 and KABP013 on bile acid (BA)
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Stem cell factor and cKIT modulate endothelial glycolysis in hypoxia Cardiovasc. Res. (IF 10.8) Pub Date : 2024-03-20 Hayoung Jeong, Ryul-I Kim, Hyunwoo Koo, Yang Hee Choi, Minju Kim, Hyejin Roh, Sang Gyu Park, Jong-Hyuk Sung, Koung Li Kim, Wonhee Suh
Aims In hypoxia, endothelial cells proliferate, migrate, and form new vasculature in a process called angiogenesis. Recent studies have suggested that endothelial cells rely on glycolysis to meet metabolic needs for angiogenesis in ischemic tissues and several studies have investigated the molecular mechanisms integrating angiogenesis and endothelial metabolism. Here, we investigated the role of stem
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Influence of angiotensin II on the gut microbiome: Modest effects in comparison to experimental factors Cardiovasc. Res. (IF 10.8) Pub Date : 2024-03-20 Rikeish R Muralitharan, Michael E Nakai, Matthew Snelson, Tenghao Zheng, Evany Dinakis, Liang Xie, Hamdi Jama, Madeleine Paterson, Waled Shihata, Flavia Wassef, Antony Vinh, Grant R Drummond, David M Kaye, Charles R Mackay, Francine Z Marques
Introduction Animal models are regularly used to test the role of the gut microbiome in hypertension. Small-scale pre-clinical studies have investigated changes to the gut microbiome in the angiotensin II hypertensive model. However, the gut microbiome is influenced by internal and external experimental factors which are not regularly considered in the study design. Once these factors are accounted
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Four-week inhibition of the renin-angiotensin system in spontaneously hypertensive rats results in persistently lower blood pressure with reduced kidney renin and changes in expression of relevant gene networks Cardiovasc. Res. (IF 10.8) Pub Date : 2024-03-19 Sean G Byars, Priscilla Prestes, Vara Suphapimol, Fumihiko Takeuchi, Nathan De Vries, Michelle C Maier, Mariana Melo, David Balding, Nilesh Samani, Andrew M Allen, Norihiro Kato, Jennifer L Wilkinson-Berka, Fadi Charchar, Stephen B Harrap
Aims Prevention of human hypertension is an important challenge and has been achieved in experimental models. Brief treatment with renin-angiotensin system (RAS) inhibitors permanently reduces the genetic hypertension of the spontaneously hypertensive rat (SHR). The kidney is involved in this fascinating phenomenon, but relevant changes in gene expression are unknown. Methods In SHR, we studied the
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Persistent increase of cardiovascular and cerebrovascular events in COVID-19 patients: a 3-year population-based analysis Cardiovasc. Res. (IF 10.8) Pub Date : 2024-03-19 Battistoni Allegra, Volpe Massimo, Morisco Carmine, Piccinocchi Gaetano, Piccinocchi Roberto, Fini Massimo, Proietti Stefania, Bonassi Stefano, Trimarco Bruno
Aim We evaluated the incidence and relative risk of major post-acute cardiovascular consequences of SARS-CoV-2 infection in a large real-world population from a primary care database in a region at moderate cardiovascular risk followed up in the period 2020-2022. Methods and results This is a retrospective cohort analysis using data from a cooperative of general practitioners in Italy. Individuals
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BMP9 is a key player in endothelial identity and its loss is sufficient to induce arteriovenous malformations Cardiovasc. Res. (IF 10.8) Pub Date : 2024-03-18 A Desroches-Castan, D Koca, H Liu, C Roelants, L Resmini, N Ricard, C Bouvard, N Chaumontel, P L Tharaux, E Tillet, C Battail, O Lenoir, S Bailly
Aims BMP9 is a high affinity ligand of ALK1 and endoglin receptors that are mutated in the rare genetic vascular disorder Hereditary Hemorrhagic Telangiectasia (HHT). We have previously shown that loss of Bmp9 in the 129/Ola genetic background leads to spontaneous liver fibrosis via capillarization of liver sinusoidal endothelial cells (LSEC) and kidney lesions. We aimed to decipher the molecular mechanisms
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SNHG18 controls vascular smooth muscle cell contractile phenotype and neointimal hyperplasia Cardiovasc. Res. (IF 10.8) Pub Date : 2024-03-18 Kaiyuan Niu, Chengxin Zhang, Mei Yang, Eithne Margaret Maguire, Zhenning Shi, Shasha Sun, Jianping Wu, Chenxin Liu, Weiwei An, Xinxin Wang, Shan Gao, Shenglin Ge, Qingzhong Xiao
Aims Long non-coding RNA (LncRNA) small nucleolar RNA host gene 18 (SNHG18) has been widely implicated in cancers. However, little is known about its functional involvement in vascular diseases. Herein, we attempted to explore a role for SNHG18 in modulating vascular smooth muscle cell (VSMC) contractile phenotype and injury-induced neointima formation. Methods and Results Analysis of single cell RNA
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SGLT2 inhibitors: from glucose-lowering to cardiovascular benefits Cardiovasc. Res. (IF 10.8) Pub Date : 2024-03-08 Alberto Preda, Fabrizio Montecucco, Federico Carbone, Giovanni G Camici, Thomas F Lüscher, Simon Kraler, Luca Liberale
An increasing number of individuals is at high risk of type 2 diabetes (T2D) and its cardiovascular complications, including heart failure (HF), chronic kidney disease (CKD), and premature death. The sodium-glucose cotransporter-2 (SGLT2) protein sits in the proximal tubule of human nephrons to regulate glucose reabsorption, and its inhibition by gliflozins represents the cornerstone of contemporary
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Smooth muscle cell-specific MMP-3 deletion reduces osteogenic transformation and medial artery calcification Cardiovasc. Res. (IF 10.8) Pub Date : 2024-03-08 Yangzhouyun Xie, Tonghui Lin, Ying Jin, Alexa G Berezowitz, Xue-Lin Wang, Jinny Lu, Yujun Cai, Raul J Guzman
Aims Vascular calcification is highly prevalent in atherosclerosis, diabetes, and chronic kidney disease. It is associated with increased morbidity and mortality in patients with cardiovascular disease. Matrix metalloproteinase 3 (MMP-3), also known as stromelysin-1, is part of the large matrix metalloproteinase family. It can degrade extracellular matrix components of the arterial wall including elastin
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The electrophysiologic effects of KCNQ1 extend beyond expression of IKs: evidence from genetic and pharmacologic block Cardiovasc. Res. (IF 10.8) Pub Date : 2024-03-05 Yuko Wada, Lili Wang, Lynn D Hall, Tao Yang, Laura L Short, Joseph F Solus, Andrew M Glazer, Dan M Roden
Aims While variants in KCNQ1 are the commonest cause of the congenital long QT syndrome, we and others find only a small IKs in cardiomyocytes from human induced pluripotent stem cells (iPSC-CMs) or human ventricular myocytes. Methods and Results We studied population control iPSC-CMs and iPSC-CMs from a patient with Jervell and Lange-Nielsen (JLN) syndrome due to compound heterozygous loss of function
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Large animal models of pressure overload-induced cardiac left ventricular hypertrophy to study remodeling of the human heart with aortic stenosis Cardiovasc. Res. (IF 10.8) Pub Date : 2024-02-29 Evangelia Beslika, Adelino Leite-Moreira, Leon J De Windt, Paula da Costa Martins
Pathologic cardiac hypertrophy is a common consequence of many cardiovascular diseases, including aortic stenosis. Aortic stenosis is known to increase the pressure load of the left ventricle, causing a compensative response of the cardiac muscle, which progressively will lead to dilation and heart failure. In a cellular level, this corresponds to a considerable increase in the size of cardiomyocytes
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Heart failure-induced microbial dysbiosis contributes to colonic tumour formation in mice Cardiovasc. Res. (IF 10.8) Pub Date : 2024-02-24 Sanne de Wit, Lotte Geerlings, Canxia Shi, Just Dronkers, Elisabeth M Schouten, Gillian Blancke, Vanessa Andries, Tess Yntema, Wouter C Meijers, Debby P Y Koonen, Lars Vereecke, Herman H W Silljé, Joseph-Pierre Aboumsallem, Rudolf A de Boer
Introduction Heart failure (HF) and cancer are the leading causes of death worldwide. Epidemiological studies revealed that HF patients are prone to develop cancer. Preclinical studies provided some insights into this connection, but the exact mechanisms remain elusive. In colorectal cancer (CRC), gut microbial dysbiosis is linked to cancer progression and recent studies have shown that HF patients
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Cardiac and perivascular myofibroblasts, matrifibrocytes, and immune fibrocytes in hypertension; commonalities and differences with myocardial infarction and other cardiovascular diseases Cardiovasc. Res. (IF 10.8) Pub Date : 2024-02-23 Keiichi Torimoto, Katherine Elliott, Yuki Nakayama, Hiromi Yanagisawa, Satoru Eguchi
Hypertension is a major cause of cardiovascular diseases such as myocardial infarction and stroke. Cardiovascular fibrosis occurs with hypertension and contributes to vascular resistance, aortic stiffness, and cardiac hypertrophy. However, the molecular mechanisms leading to the fibroblast activation in hypertension remain largely unknown. There are two types of fibrosis: replacement fibrosis and reactive
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Decreasing microtubule detyrosination modulates Nav1.5 subcellular distribution and restores sodium current in mdx cardiomyocytes Cardiovasc. Res. (IF 10.8) Pub Date : 2024-02-23 Giovanna Nasilli, Tanja M de Waal, Gerard A Marchal, Giorgia Bertoli, Marieke W Veldkamp, Eli Rothenberg, Simona Casini, Carol Ann Remme
Background The microtubule (MT) network plays a major role in the transport of the cardiac sodium channel Nav1.5 to the membrane, where the latter associates with interacting proteins such as dystrophin. Alterations in MT dynamics are known to impact on ion channel trafficking. Duchenne muscular dystrophy (DMD), caused by dystrophin deficiency, is associated with an increase in MT detyrosination, decreased
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Endothelial to mesenchymal transition: at the axis of cardiovascular health and disease Cardiovasc. Res. (IF 10.8) Pub Date : 2024-02-22 Ignacio Fernando Hall, Franceska Kishta, Yang Xu, Andrew H Baker, Jason C Kovacic
Endothelial cells (ECs) line the luminal surface of blood vessels and play a major role in vascular (patho)-physiology by acting as a barrier, sensing circulating factors and intrinsic/extrinsic signals. ECs have the capacity to undergo endothelial-to-mesenchymal transition (EndMT), a complex differentiation process with key roles both during embryonic development and in adulthood. EndMT can contribute
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Marginal zone B cells produce ‘natural’ atheroprotective IgM antibodies in a T cell–dependent manner Cardiovasc. Res. (IF 10.8) Pub Date : 2024-02-21 James Harrison, Stephen A Newland, Wei Jiang, Despoina Giakomidi, Xiaohui Zhao, Marc Clement, Leanne Masters, Andrej Corovic, Xian Zhang, Fabrizio Drago, Marcella Ma, Maria Ozsvar Kozma, Froher Yasin, Yuta Saady, Hema Kothari, Tian X Zhao, Guo-Ping Shi, Coleen A McNamara, Christoph J Binder, Andrew P Sage, Jason M Tarkin, Ziad Mallat, Meritxell Nus
Aims The adaptive immune response plays an important role in atherosclerosis. In response to a high-fat/high-cholesterol (HF/HC) diet, marginal zone B (MZB) cells activate an atheroprotective programme by regulating the differentiation and accumulation of ‘poorly differentiated’ T follicular helper (Tfh) cells. On the other hand, Tfh cells activate the germinal centre response, which promotes atherosclerosis
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LNK/SH2B3 loss of function increases susceptibility to murine and human atrial fibrillation Cardiovasc. Res. (IF 10.8) Pub Date : 2024-02-20 Matthew B Murphy, Zhenjiang Yang, Tuerdi Subati, Eric Farber-Eger, Kyungsoo Kim, Daniel J Blackwell, Matthew R Fleming, Joshua M Stark, Joseph C Van Amburg, Kaylen K Woodall, Justin P Van Beusecum, Vineet Agrawal, Charles D Smart, Ashley Pitzer, James B Atkinson, Agnes B Fogo, Julie A Bastarache, Annet Kirabo, Quinn S Wells, Meena S Madhur, Joey V Barnett, Katherine T Murray
Aims The lymphocyte adaptor protein (LNK) is a negative regulator of cytokine and growth factor signaling. The rs3184504 variant in SH2B3 reduces LNK function and is linked to cardiovascular, inflammatory, and hematologic disorders including stroke. In mice, deletion of Lnk causes inflammation and oxidative stress. We hypothesized that Lnk-/- mice are susceptible to atrial fibrillation (AF) and that
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The role of endoplasmic reticulum–mitochondria-associated membranes in diabetic kidney disease Cardiovasc. Res. (IF 10.8) Pub Date : 2024-02-17 Ahmed Elwakiel, Akash Mathew, Berend Isermann
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. The pathomechanisms of DKD are multifactorial, yet haemodynamic and metabolic changes in the early stages of the disease appear to predispose towards irreversible functional loss and histopathological changes. Recent studies highlight the importance of endoplasmic reticulum–mitochondria-associated membranes (ER-MAMs)
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Restoration of blood vessel regeneration in the era of combination SGLT2i and GLP-1RA therapy for diabetes and obesity Cardiovasc. Res. (IF 10.8) Pub Date : 2024-02-17 Daniella C Terenzi, Ehab Bakbak, Hwee Teoh, Aishwarya Krishnaraj, Pankaj Puar, Ori D Rotstein, Francesco Cosentino, Ronald M Goldenberg, Subodh Verma, David A Hess
Ischaemic cardiovascular diseases, including peripheral and coronary artery disease, myocardial infarction, and stroke, remain major comorbidities for individuals with type 2 diabetes (T2D) and obesity. During cardiometabolic chronic disease (CMCD), hyperglycaemia and excess adiposity elevate oxidative stress and promote endothelial damage, alongside an imbalance in circulating pro-vascular progenitor
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Sequestosome 1 (p62) mitigates hypoxia-induced cardiac dysfunction by stabilizing hypoxia-inducible factor 1α and nuclear factor erythroid 2-related factor 2 Cardiovasc. Res. (IF 10.8) Pub Date : 2024-02-09 Rajeshwary Ghosh, Amir Nima Fatahian, Omid M T Rouzbehani, Marissa A Hathaway, Tariq Mosleh, Vishaka Vinod, Sidney Vowles, Sophie L Stephens, Siu-Lai Desmond Chung, Isaac D Cao, Anila Jonnavithula, J David Symons, Sihem Boudina
Aims Heart failure due to ischaemic heart disease (IHD) is a leading cause of mortality worldwide. A major contributing factor to IHD-induced cardiac damage is hypoxia. Sequestosome 1 (p62) is a multi-functional adaptor protein with pleiotropic roles in autophagy, proteostasis, inflammation, and cancer. Despite abundant expression in cardiomyocytes, the role of p62 in cardiac physiology is not well
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ISG15 blocks cardiac glycolysis and ensures sufficient mitochondrial energy production during Coxsackievirus B3 infection Cardiovasc. Res. (IF 10.8) Pub Date : 2024-02-03 Clara Bredow, Fabien Thery, Eva Katrin Wirth, Sarah Ochs, Meike Kespohl, Gunnar Kleinau, Nicolas Kelm, Niclas Gimber, Jan Schmoranzer, Martin Voss, Karin Klingel, Joachim Spranger, Kostja Renko, Markus Ralser, Michael Mülleder, Arnd Heuser, Klaus-Peter Knobeloch, Patrick Scheerer, Jennifer Kirwan, Ulrike Brüning, Nikolaus Berndt, Francis Impens, Antje Beling
Aims Virus infection triggers inflammation and, may impose nutrient shortage to the heart. Supported by type I interferon (IFN) signaling, cardiomyocytes counteract infection by various effector processes, with the IFN-stimulated gene of 15 kDa (ISG15) system being intensively regulated and protein modification with ISG15 protecting mice Coxsackievirus B3 (CVB3) infection. The underlying molecular
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Translatome profiling reveals Itih4 as a novel smooth muscle cell-specific gene in atherosclerosis Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-30 Aarthi Ravindran, Lari Holappa, Henri Niskanen, Ilya Skovorodkin, Susanna Kaisto, Mustafa Beter, Miika Kiema, Ilakya Selvarajan, Valtteri Nurminen, Einari Aavik, Rédouane Aherrahrou, Sanna Pasonen-Seppänen, Vittorio Fortino, Johanna P Laakkonen, Seppo Ylä-Herttuala, Seppo Vainio, Tiit Örd, Minna U Kaikkonen
Aims Vascular smooth muscle cells (SMCs) and their derivatives are key contributors to the development of atherosclerosis. However, studying changes in SMC gene expression in heterogeneous vascular tissues is challenging due to the technical limitations and high cost associated with current approaches. In this paper, we apply Translating Ribosome Affinity Purification sequencing (TRAP-Seq) to profile
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Networks of gut bacteria relate to cardiovascular disease in a multi-ethnic population: the HELIUS study Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-30 M V Warmbrunn, U Boulund, J Aron-Wisnewsky, M C de Goffau, R E Abeka, M Davids, L R F Bresser, E Levin, K Clement, H Galenkamp, B Ferwerda, B J H van den Born, A Kurilshikov, J Fu, A H Zwinderman, M R Soeters, D H van Raalte, H Herrema, A K Groen, M Nieuwdorp
Aims Gut microbiota have been linked to blood lipid levels and cardiovascular diseases (CVD). The composition and abundance of gut microbiota trophic networks differ between ethnicities. We aim to evaluate the relationship between gut microbiotal trophic networks and CVD phenotypes. Methods and Results We included cross-sectional data from 3860 individuals without CVD history from six ethnicities living
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Why is early-onset atrial fibrillation uncommon in patients with Duchenne Muscular Dystrophy? Insights from the mdx mouse Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-25 My-Nhan Nguyen, Charlotte Hooper, Matilde Stefanini, Besarte Vrellaku, Ricardo Carnicer, Matthew J Wood, Jillian N Simon, Barbara Casadei
Background A reduction in both dystrophin and neuronal nitric oxide synthase (NOS1) secondary to microRNA-31 (miR-31) upregulation contributes to the atrial electrical remodelling that underpins human and experimental atrial fibrillation (AF). By contrast, patients with Duchenne Muscular Dystrophy (DMD), who lack dystrophin and NOS1 and, at least in the skeletal muscle, have raised miR-31 expression
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Long-term simulated microgravity fosters carotid aging-like changes via Piezo1 Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-25 Jiaxin Zhang, Xinpei Wang, Zihao Fu, Changyang Xing, Zhen Wang, Hongyan Yang, Jiahui Li, Meijie Liu, Ling Dong, Xing Zhang, Yongzhi Li, Jiaping Wang, Jiangang Long, Jiankang Liu, Shengpeng Wang, Jia Li, Feng Gao
Aims Elucidating the impacts of long-term spaceflight on cardiovascular health is urgently needed in face of the rapid development of human space exploration. Recent reports including the NASA Twins Study on vascular deconditioning and aging of astronauts in spaceflight are controversial. The aims of this study were to elucidate whether long-term microgravity promotes vascular aging and the underlying
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Ecto-CD38-NADase inhibition modulates cardiac metabolism and protects mice against Doxorubicin-induced cardiotoxicity Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-25 Thais R Peclat, Guillermo Agorrody, Laura Colman, Sonu Kashyap, Julianna D Zeidler, Claudia C S Chini, Gina M Warner, Katie L Thompson, Pranjali Dalvi, Felipe Beckedorff, Sanam Ebtehaj, Joerg Herrmann, Wim van Schooten, Eduardo Nunes Chini
Aims Doxorubicin (DXR) is a chemotherapeutic agent that causes dose-dependent cardiotoxicity. Recently it has been proposed that the NADase CD38 may play a role in doxorubicin-induced cardiotoxicity (DIC). CD38 is the main NAD+-catabolizing enzyme in mammalian tissues. Interestingly, in the heart, CD38 is mostly expressed as an ecto-enzyme that can be targeted by specific inhibitory antibodies. The
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The Kir2.1E299V mutation increases atrial fibrillation vulnerability while protecting the ventricles against arrhythmias in a mouse model of Short QT Syndrome type 3 Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-23 Ana I Moreno-Manuel, Álvaro Macías, Francisco M Cruz, Lilian K Gutiérrez, Fernando Martínez, Andrés González-Guerra, Isabel Martínez Carrascoso, Francisco José Bermúdez-Jimenez, Patricia Sánchez-Pérez, María Linarejos Vera-Pedrosa, Juan Manuel Ruiz, Juan A Bernal, José Jalife
Aims Short QT Syndrome Type 3 (SQTS3) is a rare arrhythmogenic disease caused by gain-of-function mutations in KCNJ2, the gene coding the inward rectifier potassium channel Kir2.1. We used a multidisciplinary approach and investigated arrhythmogenic mechanisms in an in-vivo model of de-novo mutation Kir2.1E299V identified in a patient presenting an extremely abbreviated QT interval and paroxysmal atrial
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Induced pluripotent stem cell–derived exosomes attenuate vascular remodelling in pulmonary arterial hypertension by targeting HIF-1α and Runx2 Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-22 Pei-Ling Chi, Chin-Chang Cheng, Mei-Tzu Wang, Jia-Bin Liao, Shu-Hung Kuo, Kun-Chang Lin, Min-Ci Shen, Wei-Chun Huang
Aims Pulmonary arterial hypertension (PAH) is characterized by extensive pulmonary arterial remodelling. Although mesenchymal stem cell (MSC)-derived exosomes provide protective effects in PAH, MSCs exhibit limited senescence during in vitro expansion compared with the induced pluripotent stem cells (iPSCs). Moreover, the exact mechanism is not known. Methods and results In this study, we used murine
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Do patients benefit from omega-3 fatty acids? Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-22 Samuel C R Sherratt, R Preston Mason, Peter Libby, Ph Gabriel Steg, Deepak L Bhatt
Omega-3 fatty acids (O3FAs) possess beneficial properties for cardiovascular (CV) health and elevated O3FA levels are associated with lower incident risk for CV disease (CVD.) Yet, treatment of at-risk patients with various O3FA formulations has produced disparate results in large, well-controlled and well-conducted clinical trials. Prescription formulations and fish oil supplements containing low-dose
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Depleting inositol pyrophosphate 5-InsP7 protected the heart against ischemia-reperfusion injury by elevating plasma adiponectin Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-22 Lin Fu, Jimin Du, David Furkert, Megan L Shipton, Xiaoqi Liu, Tim Aguirre, Alfred C Chin, Andrew M Riley, Barry V L Potter, Dorothea Fiedler, Xu Zhang, Yi Zhu, Chenglai Fu
Aims Adiponectin is an adipocyte-derived circulating protein that exerts cardiovascular and metabolic protection. Due to the futile degradation of endogenous adiponectin and the challenges of exogenous administration, regulatory mechanisms of adiponectin biosynthesis are of significant pharmacological interest. Methods and results Here, we report that 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate
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Vasostatins: new molecular targets for atherosclerosis, post-ischaemic angiogenesis, and arteriogenesis Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-20 Rosalinda Madonna, Serena Barachini, Sandra Ghelardoni, Lin Lu, Wei-Feng Shen, Raffaele De Caterina
The chromogranin–secretogranin secretory proteins—granins—are acidic proteins localized in granules of endocrine cells and neurons. The chromogranin family includes chromogranins A (CgA) and B, as well as secretogranin II (once called chromogranin C). Members of this family undergo catalytic proteolysis to produce active peptides. The CgA-derived peptides vasostatin-1 and vasostatin-2, in particular
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Hypertrophic cardiomyopathy dysfunction mimicked in human engineered heart tissue and improved by SGLT2 inhibitors Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-17 Paul J M Wijnker, Rafeeh Dinani, Nico C van der Laan, Sila Algül, Bjorn C Knollmann, Arie O Verkerk, Carol Ann Remme, Coert J Zuurbier, Diederik W D Kuster, Jolanda van der Velden
Aims Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy, often caused by pathogenic sarcomere mutations. Early characteristics of HCM are diastolic dysfunction and hypercontractility. Treatment to prevent mutation-induced cardiac dysfunction is lacking. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a group of antidiabetic drugs that recently showed beneficial cardiovascular
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Histone demethylase KDM5 regulates cardiomyocyte maturation by promoting fatty acid oxidation, oxidative phosphorylation, and myofibrillar organization Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-17 Manisha Deogharia, Leslye Venegas-Zamora, Akanksha Agrawal, Miusi Shi, Abhinav K Jain, Kevin J McHugh, Francisco Altamirano, A J Marian, Priyatansh Gurha
Aims Human pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) provide a platform to identify and characterize factors that regulate the maturation of CMs. The transition from an immature fetal to adult CM state entails coordinated regulation of the expression of genes involved in myofibril formation and OXPHOS among others. Lysine demethylase 5 (KDM5) specifically demethylate H3K4me1/2/3 and have
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Perilipin 1: a systematic review on its functions on lipid metabolism and atherosclerosis in mice and humans Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-11 Camille Desgrouas, Tabea Thalheim, Mathieu Cerino, Catherine Badens, Nathalie Bonello-Palot
The function of perilipin 1 in human metabolism was recently highlighted by the description of PLIN1 variants associated with various pathologies. These include severe familial partial lipodystrophy and early onset acute coronary syndrome. Additionally, certain variants have been reported to have a protective effect toward cardio-vascular diseases. The role of this protein remains controversial in
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Cardiac MAO-A inhibition protects against catecholamine-induced ventricular arrhythmias via enhanced diastolic calcium control Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-10 Qian Shi, Hamza Malik, Rachel M Crawford, Jennifer Streeter, Jinxi Wang, Ran Huo, Jean C Shih, Biyi Chen, Duane Hall, E Dale Abel, Long-Sheng Song, Ethan J Anderson
Aims A mechanistic link between depression and risk of arrhythmias could be attributed to altered catecholamine metabolism in the heart. Monoamine oxidase-A (MAO-A), a key enzyme involved in catecholamine metabolism and longstanding antidepressant target, is highly expressed in the myocardium. The present study aimed to elucidate the functional significance and underlying mechanisms of cardiac MAO-A
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Endothelium-specific SIRT7 targeting ameliorates pulmonary hypertension through KLF4 deacetylation Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-09 Jin Zhang, Chenzhong Xu, Xiaolong Tang, Shimin Sun, Siqi Liu, Langmei Yang, Yuqin Chen, Qifeng Yang, Tong-You Wade Wei, Xiaojing Wu, Jian Wang, Chen Wang, Xiaosong Yan, Lei Yang, Yanqin Niu, Deming Gou, John Y-J Shyy, Baohua Liu
Aims Pulmonary hypertension (PH) is a pulmonary vascular disease characterized by a high mortality rate. Pulmonary arterial endothelium cells (PAECs) serve as a primary sensor of various environmental cues, such as shear stress and hypoxia, but PAEC dysfunction may trigger vascular remodeling during the onset of PH. This study was aimed to illustrate the role of SIRT7 in endothelial dysfunction during
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Mitochondrial fatty acid oxidation is the major source of cardiac ATP production in heart failure with preserved ejection fraction Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-09 Qiuyu Sun, Berna Güven, Cory S Wagg, Amanda A de Oliveira, Heidi Silver, Liyan Zhang, Brandon Chen, Kaleigh Wei, Ezra Ketema, Qutuba G Karwi, Kaya L Persad, Jennie Vu, Faqi Wang, Jason R B Dyck, Gavin Y Oudit, Gary D Lopaschuk
Aims Heart failure with preserved ejection fraction (HFpEF) is a prevalent disease worldwide. While it is well established that alterations of cardiac energy metabolism contribute to cardiovascular pathology, the precise source of fuel used by the heart in HFpEF remain unclear. The objective of this study was to define the energy metabolic profile of the heart in HFpEF. Methods and Results 8-week-old
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The role of cellular senescence in profibrillatory atrial remodeling associated with cardiac pathology Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-05 Mozhdeh Mehdizadeh, Patrice Naud, Issam H Abu-Taha, Roddy Hiram, Feng Xiong, Jiening Xiao, Arnela Saljic, Markus Kamler, Nhung Vuong-Robillard, Eric Thorin, Gerardo Ferbeyre, Jean-Claude Tardif, Martin G Sirois, Jean Francois Tanguay, Dobromir Dobrev, Stanley Nattel
Aims Cellular senescence is a stress-related or aging response believed to contribute to many cardiac conditions; however, its role in atrial fibrillation (AF) is unknown. Age is the single most important determinant of the risk of AF. The present study was designed to: 1) Evaluate AF-susceptibility and senescence-marker expression in rat models of aging and myocardial infarction (MI); 2) Study the
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Cyclophilin A is a ligand for RAGE in thrombo-inflammation Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-04 Peter Seizer, Saskia N I von Ungern-Sternberg, Verena Haug, Valerie Dicenta, Annabelle Rosa, Elke Butt, Moritz Nöthel, Anne-Katrin Rohlfing, Manuel Sigle, Peter P Nawroth, Claudia Nussbaum, Markus Sperandio, Charly Kusch, Mara Meub, Markus Sauer, Patrick Münzer, Kristin Bieber, Anna Stanger, Andreas F Mack, René Huber, Korbinian Brand, Moritz Lehners, Robert Feil, Antti Poso, Konstantin Krutzke, Tilman
Aims Cyclophilin A (CyPA) induces leukocyte recruitment and platelet activation upon release into the extracellular space. Extracellular CyPA therefore plays a critical role in immuno-inflammatory responses in tissue injury and thrombosis upon platelet activation. To date, CD147 (EMMPRIN) has been described as the primary receptor mediating extracellular effects of CyPA in platelets and leukocytes
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Gene therapy encoding cell cycle factors to treat chronic ischemic heart failure in rats Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-03 Riham R E Abouleisa, Xian-Liang Tang, Qinghui Ou, Abou-Bakr M Salama, Amie Woolard, Dana Hammouri, Hania Abdelhafez, Sarah Cayton, Sameeha K Abdulwali, Momo Arai, Israel D Sithu, Daniel J Conklin, Roberto Bolli, Tamer M A Mohamed
Aims Gene therapies to induce cardiomyocyte (CM) cell cycle re-entry have shown a potential to treat subacute ischemic heart failure (IHF) but have not been tested in the more relevant setting of chronic IHF. Our group recently showed that polycistronic non-integrating lentivirus encoding Cdk1/CyclinB1 and Cdk4/CyclinD1 (TNNT2-4Fpolycistronic-NIL) is effective in inducing CM cell cycle re-entry and
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IKKβ stabilizes Mitofusin 2 and suppresses doxorubicin cardiomyopathy Cardiovasc. Res. (IF 10.8) Pub Date : 2024-01-02 Matthew Guberman, Rimpy Dhingra, Jenna Cross, Victoria Margulets, Hongying Gang, Inna Rabinovich-Nikitin, Lorrie A Kirshenbaum
Aims The mitochondrial dynamics protein Mitofusin 2 (MFN2) coordinates critical cellular processes including mitochondrial bioenergetics, quality control, and cell viability. The NF-κB kinase IKKβ suppresses mitochondrial injury in doxorubicin cardiomyopathy, but the underlying mechanism is undefined. Methods and results Herein, we identify a novel signalling axis that functionally connects IKKβ and
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SARS-CoV-2 induced vascular endothelial dysfunction: direct or indirect effects? Cardiovasc. Res. (IF 10.8) Pub Date : 2023-12-29 Kathy O Lui, Zhangjing Ma, Stefanie Dimmeler
Clinical evidence reveals that manifestations of endothelial dysfunction are widely observed in COVID-19 and long-COVID patients. However, whether these detrimental effects are caused by direct infection of the endothelium or are indirectly mediated by systemic inflammation has been a matter of debate. It has been well acknowledged that endothelial cells (ECs) of the cardiovascular system ubiquitously
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Sphingosine-1-phosphate receptor 3 regulates the transendothelial transport of HDL and LDL in opposite ways Cardiovasc. Res. (IF 10.8) Pub Date : 2023-12-16 Srividya Velagapudi, Dongdong Wang, Francesco Poti, Renata Feuerborn, Jerome Robert, Eveline Schlumpf, Mustafa Yalcinkaya, Grigorios Panteloglou, Anton Potapenko, Manuela Simoni, Lucia Rohrer, Jerzy-Roch Nofer, Arnold von Eckardstein
Aims The entry of lipoproteins from blood into the arterial wall is a rate-limiting step in atherosclerosis. It is controversial whether this happens by filtration or regulated transendothelial transport. Because sphingosine-1-phosphate (S1P) preserves the endothelial barrier, we investigated in vivo and in vitro, whether S1P and its cognate S1P receptor 3 (S1P3) regulate the transendothelial transport
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Remodelling of cAMP dynamics within the SERCA2a microdomain in heart failure with preserved ejection fraction caused by obesity and type 2 diabetes Cardiovasc. Res. (IF 10.8) Pub Date : 2023-12-12 Ping Lai, Susanne S Hille, Hariharan Subramanian, Robert Weigman, Pia Roser, Oliver J Müller, Viacheslav O Nikolaev, Kirstie A De Jong
Aims Despite massive efforts, we remain far behind in our attempts to identify effective therapies to treat heart failure with preserved ejection fraction (HFpEF). Diastolic function is critically regulated by sarcoplasmic/endoplasmic reticulum (SR) calcium ATPase 2a (SERCA2a) which forms a functional cardiomyocyte (CM) microdomain where 3’,5’-cyclic adenosine monophosphate (cAMP) produced upon β-adrenoceptor
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An inflammation resolution-promoting intervention prevents atrial fibrillation due to left-ventricular dysfunction Cardiovasc. Res. (IF 10.8) Pub Date : 2023-12-12 Roddy Hiram, Feng Xiong, Patrice Naud, Jiening Xiao, Deanna K Sosnowski, Ewen Le Quilliec, Arnela Saljic, Issam H Abu-Taha, Markus Kamler, Charles-Alexandre LeBlanc, Doa’a G F Al-U’Datt, Martin G Sirois, Terence Hebert, Jean-François Tanguay, Jean-Claude Tardif, Dobromir Dobrev, Stanley Nattel
Aims Recent studies suggest that bioactive mediators called resolvins promote active resolution of inflammation. Inflammatory signaling is involved in development of the substrate for atrial fibrillation (AF). To evaluate effects of resolvin-D1 on atrial arrhythmogenic remodeling resulting from left-ventricular dysfunction induced by myocardial infarction (MI) in rats. Methods and Results MI was produced