BACKGROUND Perivascular adipose tissue (PVAT) is a key regulator of vascular dysfunction. Impairment of PVAT phenotypic plasticity with aging may play a role in vascular pathology including abdominal aortic aneurysms (AAAs). Yet, the mechanisms underlying PVAT plasticity in aneurysm pathogenesis remain elusive. METHODS Single-cell RNA sequencing was performed on perivascular stromal cells from young

BACKGROUND In sickle cell disease (SCD), erythrocyte reactive oxygen species (ROS) production and oxidative stress play a critical role in vaso-occlusion, a hallmark of SCD. Small noncoding nucleolar RNAs (snoRNAs) of the Rpl13a locus have been described as regulators of ROS levels. However, whether Rpl13a snoRNAs are present in sickle red blood cells (RBCs) and regulate ROS levels and whether they

BACKGROUND Aortic dissection (AD) is the separation of medial layers of the aorta and is a major cause of death in patients with connective tissue disorders such as Marfan syndrome. However, molecular triggers instigating AD, its temporospatial progression, and how vascular cells in each vessel layer interact and participate in the pathological process remain incompletely understood. To unravel the

BACKGROUND The fatty acid (FA) transporter CD36 (FA translocase/cluster of differentiation 36) is the gatekeeper of cardiac FA metabolism. Preferential localization of CD36 to the sarcolemma is one of the initiating cellular responses in the development of muscle insulin resistance and the type 2 diabetic heart. Posttranslational S-acylation controls protein trafficking, and in this study, we hypothesized

BACKGROUND FXII (coagulation factor XII) is best known for its roles in the contact and kallikrein-kinin pathways. FXII is converted to its active enzyme (FXIIa [activated factor XII]) by PKa (plasma kallikrein) or its unique ability to autoactivate on bacterial or other biologic surfaces. In vivo, FXIIa initiates the intrinsic coagulation pathway and promotes inflammation by reciprocal activation

BACKGROUND Pulmonary hypertension (PH) is a lethal disease characterized in part by progressive pulmonary arteriole (PA) remodeling. Excessive PA fibrosis and macrophage infiltration are often present in PH, but the potential associations are obscure. We investigated the link between interstitial macrophage (iMΦ) infiltration and PA fibrosis in PH and idiopathic pulmonary arterial hypertension. METHODS

BACKGROUND Clinical management of heart failure with preserved ejection fraction (HFpEF) is hindered by a lack of disease-modifying therapies capable of altering its distinct pathophysiology. Despite the widespread implementation of a 2-hit model of cardiometabolic HFpEF to inform precision therapy, which utilizes ad libitum high-fat diet and 0.5% N(ω)-nitro-L-arginine methyl ester, we observe that

Angiogenesis, the formation of new blood vessels, is a fundamental biological process with implications for both physiological functions and pathological conditions. While the transcriptional regulation of angiogenesis, mediated by factors such as HIF-1α (hypoxia-inducible factor 1-alpha) and VEGF (vascular endothelial growth factor), is well-characterized, the translational regulation of this process

BACKGROUND It has become evident that some women develop preeclampsia despite aspirin. This study aimed to examine how such aspirin nonresponsiveness develops in high-risk preeclampsia pregnancies by exploring the role of genetic polymorphisms and aspirin metabolism. METHODS The study involved pregnant women who developed preeclampsia despite low-dose aspirin and those who did not. First, we conducted

BACKGROUND Preeclampsia is a placenta-origin pregnancy complication. Although its development has long been divided into 2 stages: abnormal placentation (stage I) and the release of factors from the hypoperfused placenta into circulation, triggering preeclampsia due to endothelial dysfunction (stage II), the placenta-derived substances coupling the 2 stages remain unclear. METHODS Extracellular vesicles

BACKGROUND Exercise augments hemodynamic shear to activate mechano-sensitive molecular transducers in the vascular endothelium. Recently, the central nervous system has been reported to mediate neuroimmune interaction in the aortic adventitia (AA). Whether exercise modulates the sympathetic nerve interaction with the immune cells to mitigate aortic stiffness remains unknown. METHODS AND RESULTS Four

BACKGROUND Angiogenesis is a dynamic process fine-tuned by transcription factors in endothelial cells. The KLF15 (Krüppel-like factor 15)-mediated transcriptional regulation mechanism is critical for cardiovascular diseases. However, the role of KLF15 in governing angiogenesis remains unknown. METHODS KLF15 and VASN (vasorin) were deleted from endothelial cells using tamoxifen-inducible Cdh5 promoter-driven

Malignant ventricular arrhythmias (VAs), such as ventricular tachycardia and ventricular fibrillation, are the cause of approximately half a million deaths per year in the United States, which is a common lethal event in heart disease, such as hypertension, catecholaminergic polymorphic ventricular tachycardia, takotsubo cardiomyopathy, long-QT syndrome, and progressing into advanced heart failure

BACKGROUND RBM20 (RNA binding motif protein 20) cardiomyopathy is a severe form of dilated cardiomyopathy (DCM). Genetic variants in the nuclear localization signal of Rbm20 hinder its nuclear import and promote cytoplasmic pathogenic RNP (ribonucleoprotein) granules. We aimed to investigate whether reducing RNP granules by inhibiting Rbm20 expression could alleviate the DCM phenotype in Rbm20 S639G

BACKGROUND Circular RNAs (circRNAs) have been gradually revealed to regulate the progression of heart disease in depth, showing their clinical significance. However, a mass of cardiac circRNAs still has not been functionally characterized. We aimed to explore the potential candidates that are involved in pathological cardiac hypertrophy. METHODS Public substantial RNA-sequencing data of cardiac circRNAs

BACKGROUND Pulmonary venous remodeling is a key pathological feature of pulmonary hypertension associated with left heart disease (PH-LHD). This study aims to investigate the role of regulatory T (Treg) cells in this process. METHODS We used mouse models with transverse aortic constriction and cell depletion of Foxp3-DTR/tdTomato mice to examine Treg cells' function around pulmonary veins in PH-LHD

BACKGROUND Heart failure with preserved ejection fraction (HFpEF) has overtaken heart failure with reduced ejection fraction as the leading type of heart failure globally and is marked by high morbidity and mortality rates, yet with only a single approved pharmacotherapy: SGLT2i (sodium-glucose co-transporter 2 inhibitor). A prevailing theory for the mechanism underlying SGLT2i is nutrient deprivation

BACKGROUND Cardiometabolic heart failure with preserved ejection fraction (cHFpEF) is a highly prevalent and deadly condition. Histone 3 trimethylation at lysine 36 (H3k36me3)-a chromatin signature induced by the histone methyltransferase SETD2 (SET domain containing 2)-correlates with changes in gene expression in human failing hearts; however, its role remains poorly understood. This study investigates

Clearance of circulating plasma LDL (low-density lipoprotein) cholesterol by the liver requires hepatic LDLR (low-density lipoprotein receptor). Complete absence of functional LDLR manifests in severe hypercholesterolemia and premature atherosclerotic cardiovascular disease. Since the discovery of the LDLR 50 years ago by Brown and Goldstein, all approved lipid-lowering medications have been aimed

BACKGROUND Mouse models of myocardial ischemia with subsequent heart failure are common approaches to examine heart failure pathology and possible treatment strategies. We sought to establish a high-throughput approach for echocardiography-guided induction of myocardial ischemia/reperfusion (IR) in mice. METHODS After visualization of the left coronary artery with high-resolution ultrasound imaging

BACKGROUND Individuals with diabetes are susceptible to cardiac dysfunction and heart failure, potentially resulting in mortality. Metabolic disorders frequently occur in patients with diabetes, and diabetes usually leads to remodeling of heart structure and cardiac dysfunction. However, the contribution and underlying mechanisms of metabolic and structural coupling in diabetic cardiac dysfunction

BACKGROUND Pulmonary hypertension (PH) is a life-threatening and progressive yet incurable disease. The hallmarks of PH comprise (1) sustained contraction and (2) excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs). A major stimulus to which PASMCs are exposed during PH development is altered mechanical stress, originating from increased blood pressure, changes in blood flow

BACKGROUND Cholesterol is critical for mitochondrial membrane structure and function. Given the emergence of mitochondria as a key factor in the pathogenesis of heart failure, mitochondrial cholesterol homeostasis may be crucial for maintaining mitochondrial properties and thus cardiac function. We previously showed that CM-Pcsk9-/- mice (mice with cardiomyocyte-specific deletion of the gene encoding

BACKGROUND Circulating monocytes largely contribute to macrophage buildup in atheromata, which is crucial for clearing subendothelial LDLs (low-density lipoproteins) and dead cells; however, the transitional trajectory from monocytes to macrophages in atherosclerotic plaques and the underlying regulatory mechanism remain unclear. Moreover, the role of alternative polyadenylation, a posttranscriptional

Cardiac fibrosis, a hallmark of heart failure and various cardiomyopathies, represents a complex pathological process that has long challenged therapeutic intervention. High-throughput omics technologies have begun revolutionizing our understanding of the molecular mechanisms driving cardiac fibrosis and are providing unprecedented insights into its heterogeneity and progression. This review provides

Hemodynamic shear stress, the frictional force exerted by blood flow on the endothelium, mediates vascular homeostasis. This review examines the biophysical nature and biochemical effects of shear stress on endothelial cells, with a particular focus on its impact on cardiovascular pathophysiology. Atherosclerosis develops preferentially at arterial branches and curvatures, where disturbed flow patterns

BACKGROUND Previous clinical studies have indicated reduced circulating mucosal-associated invariant T (MAIT) cells in individuals with coronary artery disease. However, the precise role and underlying mechanisms of MAIT cells in this context remain unclear. Immune homeostasis plays a pivotal role in the development of atherosclerosis. This study explores the impact of MAIT cells on atherosclerosis

BACKGROUND Cerebrovascular malformations are a pivotal cause of hemorrhage and neurological disability alongside lacking effective medication. Thyroid hormones (THs), including thyroxine and triiodothyronine, are essential for vascular development, yet whether they participate in malformed cerebrovascular pathology remains elusive. METHODS Single-cell transcriptome analysis characterized human cerebral

BACKGROUND Arrhythmogenic right ventricular cardiomyopathy type 5 (ARVC5) is the most aggressive type of ARVC, caused by a fully penetrant missense mutation (p.S358L) in TMEM43 (transmembrane protein 43). Pathologically, the disease is characterized by dilation of the cardiac chambers and fibrofatty replacement of the myocardium, which results in heart failure and sudden cardiac death. Current therapeutic

Multifaceted disparities exist between men and women with thoracic aortic aneurysm and dissection. Despite a higher prevalence of thoracic aortic aneurysm and dissection among men, women experience disproportionately accelerated aneurysmal expansion, greater risks of rupture or dissection, and acute aortic syndromes that occur at relatively smaller diameters. In the context of acute type A aortic dissection

Women face unique barriers to equitable health care. To ensure access to quality cardiovascular care across the lifespan of women, several systemic and social challenges need to be addressed. With the understanding that women often direct health care decisions, not only for themselves but for their family unit as well, a holistic approach to address health care barriers is warranted. This review aims

Cardiovascular disease is the leading cause of maternal mortality in the United States, with the majority of deaths stemming from preventable causes. Contraception is one of the tools that can be utilized to prevent mortality and morbidity associated with unplanned pregnancy in patients with underlying congenital or acquired heart disease. There are a wide range of contraceptive methods available.

Medical and surgical advancements of the past 70 years have resulted in a remarkable shift in the natural history of congenital heart disease (CHD) such that survival to adulthood is expected for >90% of children born with congenital heart defects, including those with complex CHD. There are now more adults than children living with CHD, a majority of them are female. As significant strides have been

Neurocardiology is an interdisciplinary field that examines the complex interactions between the nervous and the cardiovascular systems, exploring how neurological processes, such as autonomic nervous system regulation and brain-heart communication impact heart function and contribute to cardiovascular health and disease. Although much of the focus on cardiovascular health has centered on traditional

Preeclampsia is a syndrome of hypertension in association with target organ dysfunction, including proteinuria, which manifests during pregnancy and the immediate postpartum period. The pathophysiology of preeclampsia originates from impaired trophoblastic invasion of the placental resulting in malperfusion and involves multiple mechanistic pathways that include anti-angiogenic factors, endothelial

Obesity in women is a significant public health issue with serious implications for cardiovascular-kidney-metabolic syndrome and cardiovascular disease. This complex challenge is influenced by physiological, hormonal, socioeconomic, and cultural factors. Women face unique weight management challenges due to hormonal changes during pregnancy, perimenopause, and menopause, which affect fat distribution

BACKGROUND Aortic aneurysm/dissection (AAD) is a life-threatening disease lacking effective pharmacological treatment. Protein ubiquitination plays a pivotal role in cardiovascular diseases. However, the possible contribution of the E3 ubiquitin ligase March2 (membrane-associated RING [really interesting new gene] finger protein 2) to the cause of AAD remains elusive. METHODS Integrated single-cell

BACKGROUND Atherosclerosis is characterized by the accumulation of fatty and fibrotic plaques, which preferentially develop at curvatures and branches along the arterial trees that are exposed to disturbed flow. However, the mechanisms by which endothelial cells sense disturbed flow are still unclear. METHODS The partial carotid ligation mouse model was used to investigate disturbed flow-induced atherogenesis

BACKGROUND Endothelial cell (EC) dysfunction and vascular inflammation are critical in the initiation and progression of atherosclerosis. Long noncoding RNAs play a critical role in vascular pathology, but relatively little is known about their involvement in controlling vascular inflammation. MIR181A1HG is a conserved long noncoding RNA located in juxtaposition with miR-181a1 and miR-181b1, both involved

BACKGROUND Mounting evidence indicates that nuclear receptors play a critical regulatory role in platelet pathophysiology and thrombotic disorders. Although NR4A (the nuclear receptor subfamily 4 group A) plays an important role in cardiovascular pathophysiology, the expression profile and biological function of NR4A member 1 (NR4A1) in platelets have never been reported. METHODS We evaluated the functions