BACKGROUND Sarcolemmal small conductance Ca2+-activated K+ channels have the unique capacity to translate intracellular Ca2+ signal into repolarization, while mitochondrial SK channels can link Ca2+ cycling to mitochondrial function. We hypothesize that pharmacological enhancement of SK channels can be protective against malignant cardiac arrhythmias associated with disturbances in Ca2+ handling machinery

BACKGROUND Pulmonary artery endothelial cell (PAEC) dysfunction is a pathological hallmark of pulmonary hypertension (PH). Yet, the roles of long noncoding RNAs (lncRNAs) driven by super-enhancers (SEs) in PAECs are not well understood. In this study, we focused on the PAEC-specific SE-associated lncRNA HCG20 (HLA complex group 20) and to elucidate its role and underlying mechanisms in the progression

Heart failure afflicts >6 million individuals in the United States alone and is associated with significant mortality (≈40% within 5 years of diagnosis) and cost (estimated to exceed $70 billion in the United States by 2030). Obesity is a major risk factor for the development of heart failure. The contribution of excess adipose tissue to heart failure pathogenesis is multifactorial. For example, adipose

Cardiovascular-kidney-metabolic syndrome is a progressive disorder driven by perturbed interorgan crosstalk among adipose, liver, kidney, and heart, leading to multiorgan dysfunction. Capturing the complexity of human cardiovascular-kidney-metabolic syndrome pathophysiology using conventional models has been challenging. Multi-organ-on-a-chip platforms offer a versatile means to study underlying interorgan

Cardiovascular diseases including atherosclerosis and heart failure, arise from the intricate interplay of metabolic, immune, and neural dysregulation within vascular and cardiac tissues: This review focuses on integrating recent advances in metabolic and immune crosstalk of the cardiac vasculature that affects cardiometabolic health and disease progression. Coronary and lymphatic endothelial cells

Although the neurocardiac axis is central to cardiovascular homeostasis, its dysregulation drives heart failure and cardiometabolic diseases. This review examines the bidirectional interplay between the autonomic nervous system and the heart, highlighting the role of this interplay in disease progression and its therapeutic potential. The autonomic nervous system modulates cardiac function and vascular

Heart failure (HF) often coexists with cancer. Beyond the known cardiotoxicity of some cancer treatments, HF itself has been associated with increased cancer incidence. The 2 conditions share common risk factors, mechanisms, and interactions that can worsen patient outcomes. The bidirectional relationship between HF and cancer presents a complex interplay of factors that are not fully understood. Recent

The liver and heart are closely interconnected organs, and their bidirectional interaction plays a central role in cardiometabolic disease. In this review, we summarize current evidence linking liver dysfunction-particularly metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and cirrhosis-with an increased risk of heart failure and other cardiovascular diseases

The heart does not work in isolation, with cardiac health and disease occurring through complex interactions between the heart with multiple organs. Furthermore, the integration of organ-specific lipid metabolism, blood pressure, insulin sensitivity, and inflammation involves a complex network of signaling pathways between many organs. Dysregulation in these communications is now recognized as a key

Chronic kidney disease (CKD) represents a global health issue with a high socioeconomic impact. Beyond a progressive decline of kidney function, patients with CKD are at increased risk of cardiovascular diseases, including heart failure (HF) and sudden cardiac death. HF in CKD can manifest both as HF with reduced ejection fraction and HF with preserved ejection fraction, with the latter further increasing

Over the past few decades, the rising burden of metabolic disease, including type 2 diabetes, prediabetes, obesity, and metabolic dysfunction-associated steatotic liver disease, has corresponded with fundamental shifts in the landscape of heart failure (HF) epidemiology, including the rising prevalence of HF with preserved ejection fraction. It has become increasingly important to understand the role

Heart failure is a global health issue with significant mortality and morbidity. There is increasing evidence that alterations in the gastrointestinal microbiome, gut epithelial permeability, and gastrointestinal disorders contribute to heart failure progression through various pathways, including systemic inflammation, metabolic dysregulation, and modulation of cardiac function. Moreover, several

Physical exercise is critical for preventing and managing chronic conditions, such as cardiovascular disease, type 2 diabetes, hypertension, and sarcopenia. Regular physical activity significantly reduces cardiovascular and all-cause mortality. Exercise also enhances metabolic health by promoting muscle growth, mitochondrial biogenesis, and improved nutrient storage while preventing age-related muscle

Cardiometabolic diseases encompass a group of conditions characterized by metabolic and inflammatory abnormalities that increase the risk of diabetes and cardiovascular disease. These syndromes involve multiple organs, including the heart, arterial system, brain, skeletal muscle, adipose tissue, hematopoietic system, liver, kidneys, and pancreas. The crosstalk between these organs contributes to the

Aging processes underlie common chronic cardiometabolic diseases such as heart failure and diabetes. Cross-organ/tissue interactions can accelerate aging through cellular senescence, tissue wasting, accelerated atherosclerosis, increased vascular stiffness, and reduction in blood flow, leading to organ remodeling and premature failure. This interorgan/tissue crosstalk can accelerate aging-related dysfunction

Heart failure is the final outcome of most cardiovascular diseases and shares risk factors with other cardiovascular pathologies. Among these, inflammation plays a central role in disease progression and myocardial remodeling. Over the past 2 decades, numerous studies have explored immune-related mechanisms in cardiovascular disease, highlighting the importance of immune cross-talk between the heart

BACKGROUND Elevated levels of IgE are implicated in pathological cardiac remodeling. However, the origin of IgE remains unknown. In the current study, we aim to explore the source of IgE and the mechanisms underlying IgE production in the context of pathological cardiac remodeling. METHODS Flow cytometry was used to assess the changes of IgE-producing B cells in different organs/tissues, including

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