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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
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miR-222 inhibits pathological cardiac hypertrophyand heart failure Cardiovasc. Res. (IF 10.8) Pub Date : 2023-12-12 Xiaojun Liu, Haobo Li, Margaret H Hastings, Chunyang Xiao, Federico Damilano, Colin Platt, Carolin Lerchenmüller, Han Zhu, Xin Paul Wei, Ashish Yeri, Patrick Most, Anthony Rosenzweig
Aims Physiological cardiac hypertrophy occurs in response to exercise and can protect against pathological stress. In contrast, pathological hypertrophy occurs in disease and often precedes heart failure. The cardiac pathways activated in physiological and pathological hypertrophy are largely distinct. Our prior work demonstrated that miR-222 increases in exercised hearts and is required for exercise-induced
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Dysregulated iron homeostasis in dystrophin-deficient cardiomyocytes: correction by gene editing and pharmacological treatment Cardiovasc. Res. (IF 10.8) Pub Date : 2023-12-08 Kalina Andrysiak, Gabriela Machaj, Dominik Priesmann, Olga Woźnicka, Alicja Martyniak, Guillem Ylla, Marcus Krüger, Elżbieta Pyza, Anna Potulska-Chromik, Anna Kostera-Pruszczyk, Agnieszka Łoboda, Jacek Stępniewski, Józef Dulak
Aims Duchenne muscular dystrophy (DMD)-associated cardiomyopathy is a serious life-threatening complication, the mechanisms of which have not been fully established, and therefore no effective treatment is currently available. The purpose of the study was to identify new molecular signatures of the cardiomyopathy development in DMD. Methods and Results For modelling of DMD-associated cardiomyopathy
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“Trapped reentry” as source of acute focal atrial arrhythmias Cardiovasc. Res. (IF 10.8) Pub Date : 2023-12-04 Tim De Coster, Alexander S Teplenin, Iolanda Feola, Cindy I Bart, Arti A Ramkisoensing, Bram L den Ouden, Dirk L Ypey, Serge A Trines, Alexander V Panfilov, Katja Zeppenfeld, Antoine A F de Vries, Daniël A Pijnappels
Aims Diseased atria are characterized by functional and structural heterogeneities, adding to abnormal impulse generation and propagation. These heterogeneities are thought to lie at the origin of fractionated electrograms recorded during sinus rhythm (SR) in atrial fibrillation (AF) patients and are assumed to be involved in the onset and perpetuation (e.g. by reentry) of this disorder. The underlying
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Proinflammatory cytokines driving cardiotoxicity in Covid-19 Cardiovasc. Res. (IF 10.8) Pub Date : 2023-12-01 Maria Colzani, Johannes Bargehr, Federica Mescia, Eleanor Williams, Vincent Knight-Schrijver, Jonathan Lee, Charlotte Summers, Irina Mohorianu, Kenneth G C Smith, Paul A Lyons, Sanjay Sinha
Aims Cardiac involvement is common in patients hospitalised with COVID-19 and correlates with an adverse disease trajectory. While cardiac injury has been largely attributed to direct viral cytotoxicity, serum-induced cardiotoxicity secondary to serological hyperinflammation constitutes a potentially amenable mechanism that remains largely unexplored. Methods and results To investigate serological
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Exploring apolipoprotein C-III: Pathophysiological and pharmacological relevance Cardiovasc. Res. (IF 10.8) Pub Date : 2023-12-01 Chris J Packard, Angela Pirillo, Sotirios Tsimikas, Brian A Ference, Alberico L Catapano
The availability of pharmacological approaches able to effectively reduce circulating low-density lipoprotein cholesterol (LDL-C) has led to a substantial reduction in the risk of atherosclerosis-related cardiovascular disease. However, a residual cardiovascular risk persists in treated individuals with optimal levels of LDL-C. Additional risk factors beyond LDL-C are involved and among these, elevated
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Global prevalence of cardiovascular risk factors based on the Life's Essential 8 score: an overview of systematic reviews and meta-analysis Cardiovasc. Res. (IF 10.8) Pub Date : 2023-11-29 Rubén López-Bueno, Rodrigo Núñez-Cortés, Joaquín Calatayud, Joaquín Salazar-Méndez, Fanny Petermann-Rocha, José Francisco López-Gil, Borja del Pozo Cruz
Cardiovascular health (CVH) is a critical issue for global health. However, no previous study has determined the prevalence of cardiovascular risk factors based on the American Heart Association´s (AHA) Life’s Essential 8 (LE8). Therefore, we aimed to estimate the global prevalence of the eight cardiovascular risk factors identified in the LE8. A systematic search of systematic reviews with meta-analysis
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Complete revascularization for acute coronary syndrome, one step at a time. Cardiovasc. Res. (IF 10.8) Pub Date : 2023-11-25 Tsung-Ying Tsai,Patrick W Serruys
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Epicardioids: a novel tool for cardiac regeneration research? Cardiovasc. Res. (IF 10.8) Pub Date : 2023-11-25 Carolina Balbi,Nicola Smart
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Global accord on the integration of artificial intelligence in medical science publishing: implications of the Bletchley Declaration. Cardiovasc. Res. (IF 10.8) Pub Date : 2023-11-23 Tomasz J Guzik,Arkadiusz Sitek
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Interferon-gamma signs off an old heart. Cardiovasc. Res. (IF 10.8) Pub Date : 2023-11-15 Daniel Harding,Federica Marelli-Berg
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Should we resurrect acetazolamide as a diuretic for congestion due to heart failure? Cardiovasc. Res. (IF 10.8) Pub Date : 2023-11-15 Joe J Cuthbert,John G F Cleland
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Iron deficiency in myocardial ischaemia: molecular mechanisms and therapeutic perspectives. Cardiovasc. Res. (IF 10.8) Pub Date : 2023-11-15 Francesco Corradi,Gabriele Masini,Tonino Bucciarelli,Raffaele De Caterina
Systemic iron deficiency (SID), even in the absence of anaemia, worsens the prognosis and increases mortality in heart failure (HF). Recent clinical-epidemiological studies, however, have shown that a myocardial iron deficiency (MID) is frequently present in cases of severe HF, even in the absence of SID and without anaemia. In addition, experimental studies have shown a poor correlation between the
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Can a genetic mutation associated with glycosuria teach us about the action of sodium-glucose cotransporter-2 inhibitors? Cardiovasc. Res. (IF 10.8) Pub Date : 2023-11-15 Jonathan Golledge
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Crosstalk of platelets with macrophages and fibroblasts aggravates inflammation, aortic wall stiffening and osteopontin release in abdominal aortic aneurysm Cardiovasc. Res. (IF 10.8) Pub Date : 2023-11-15 M U Wagenhäuser, J Mulorz, K J Krott, A Ehrenberg, T Feige, Y H Rhee, M Chatterjee, N Petzold, C Böddeker, W Ibing, I Krüger, A M Popovic, J M Spin, P S Tsao, A Roseman, H Schelzig, M Elvers
Aims Abdominal aortic aneurysm (AAA) is a highly lethal disease with progressive dilatation of the abdominal aorta accompanied by degradation and remodelling of the vessel wall due to chronic inflammation. Platelets play an important role in cardiovascular diseases but their role in AAA is poorly understood. Methods and Results The present study revealed that platelets play a crucial role in promoting
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Acute heart failure: mechanisms and pre-clinical models—a Scientific Statement of the ESC Working Group on Myocardial Function Cardiovasc. Res. (IF 10.8) Pub Date : 2023-11-15 Michele Ciccarelli, Inês Falcão Pires, Johann Bauersachs, Luc Bertrand, Christophe Beauloye, Dana Dawson, Nazha Hamdani, Denise Hilfiker-Kleiner, Linda W van Laake, Frank Lezoualc’h, Wolfgang A Linke, Ida G Lunde, Peter P Rainer, Antonella Rispoli, Valeria Visco, Albino Carrizzo, Matteo Dal Ferro, Davide Stolfo, Jolanda van der Velden, Serena Zacchigna, Stephane Heymans, Thomas Thum, Carlo Gabriele
While chronic heart failure (CHF) treatment has considerably improved patient prognosis and survival, the therapeutic management of acute heart failure (AHF) has remained virtually unchanged in the last decades. This is partly due to the scarcity of pre-clinical models for the pathophysiological assessment and, consequently, the limited knowledge of molecular mechanisms involved in the different AHF
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Targeting the apelin system for the treatment of cardiovascular diseases Cardiovasc. Res. (IF 10.8) Pub Date : 2023-11-13 Fiona A Chapman, Janet J Maguire, David E Newby, Anthony P Davenport, Neeraj Dhaun
Cardiovascular disease is the leading cause of death worldwide. Its prevalence is rising due to ageing populations and the increasing incidence of diseases such as chronic kidney disease, obesity and diabetes which are associated with elevated cardiovascular risk. Despite currently available treatments, there remains a huge burden of cardiovascular disease-associated morbidity for patients and healthcare
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Contractility measurements for cardiotoxicity screening with ventricular myocardial slices of pigs Cardiovasc. Res. (IF 10.8) Pub Date : 2023-11-07 Runzhu Shi, Marius Reichardt, Dominik J Fiegle, Linda K Küpfer, Titus Czajka, Zhengwu Sun, Tim Salditt, Andreas Dendorfer, Thomas Seidel, Tobias Bruegmann
Aims Cardiotoxicity is one major reason why drugs do not enter or are withdrawn from the market. Thus, approaches are required to predict cardiotoxicity with high specificity and sensitivity. Ideally, such methods should be performed within intact cardiac tissue with high relevance for humans and detect acute and chronic side effects on electrophysiological behaviour, contractility, and tissue structure
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The inhibition of inner mitochondrial fusion in hepatocytes reduces NAFL and improves metabolic profile during obesity by modulating bile acid conjugation Cardiovasc. Res. (IF 10.8) Pub Date : 2023-11-03 Lorenzo Da Dalt, Annalisa Moregola, Monika Svecla, Silvia Pedretti, Francesca Fantini, Mirko Ronzio, Patrizia Uboldi, Diletta Dolfini, Elena Donetti, Andrea Baragetti, Nico Mitro, Luca Scorrano, Giuseppe Danilo Norata
Background and aim Mitochondria are plastic organelles that continuously undergo biogenesis, fusion, fission, and mitophagy to control cellular energy metabolism, calcium homeostasis, hormones, sterols and bile acids (BAs) synthesis. Here we evaluated how the impairment of mitochondrial fusion in hepatocytes affect diet induced liver steatosis and obesity. Methods and Results Male mice selectively
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Deletion of adipocyte NOS3 potentiates high-fat diet-induced hypertension and vascular remodeling via chemerin Cardiovasc. Res. (IF 10.8) Pub Date : 2023-10-28 Andy W C Man, Yawen Zhou, Gisela Reifenberg, Alica Camp, Thomas Münzel, Andreas Daiber, Ning Xia, Huige Li
Aims Obesity is an epidemic that is a critical contributor to hypertension and other cardiovascular diseases. Current paradigms suggest that endothelial nitric oxide synthase (eNOS/NOS3) in the vessel wall is the primary regulator of vascular function and blood pressure. However, recent studies have revealed the presence of eNOS/NOS3 in the adipocytes of white adipose tissues and perivascular adipose
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Exercise-induced circular RNA circUtrn is required for cardiac physiological hypertrophy and prevents myocardial ischemia-reperfusion injury Cardiovasc. Res. (IF 10.8) Pub Date : 2023-10-28 Lijun Wang, Jingyi Feng, Xing Feng, Danni Meng, Xuan Zhao, Jiaqi Wang, Pujiao Yu, Gui-e Xu, Meiyu Hu, Tianhui Wang, H Immo Lehmann, Guoping Li, Joost P G Sluijter, Junjie Xiao
Aims Regular exercise training benefits cardiovascular health and effectively reduces the risk for cardiovascular disease. Circular RNAs (circRNAs) play important roles in cardiac pathophysiology. However, the role of circRNAs in response to exercise training and biological mechanisms responsible for exercise-induced cardiac protection remain largely unknown. Methods and results RNA sequencing was
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Plasma adiponectin levels and risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction: large scale observational and Mendelian randomization evidence Cardiovasc. Res. (IF 10.8) Pub Date : 2023-10-27 Maria Booth Nielsen, Yunus Çolak, Marianne Benn, Amy Mason, Stephen Burgess, Børge Grønne Nordestgaard
Aims Adiponectin may play an important protective role in heart failure and associated cardiovascular diseases. We hypothesized that plasma adiponectin is associated observationally and causally, genetically with risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction. Methods and results In the Copenhagen General Population Study, we examined 30,045 individuals
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Efficacy of pharmacological and interventional treatment for resistant hypertension-a network meta-analysis Cardiovasc. Res. (IF 10.8) Pub Date : 2023-10-27 Zhejia Tian, Clara Vollmer Barbosa, Hannah Lang, Johann Bauersachs, Anette Melk, Bernhard M W Schmidt
Aims Resistant hypertension is associated with a high risk of cardiovascular disease, chronic kidney disease and mortality. Yet, its management is challenging. This study aims to establish the comparative effectiveness of pharmacologic and interventional treatments by conducting a network meta-analysis. Methods and Results MEDLINE, Cochrane Register of Controlled Trials and Web of Science Core Collection