Regulation of cardiomyocyte t-tubule structure by preload and afterload: Roles in cardiac compensation and decompensation.

Mechanical load is a potent regulator of cardiac structure and function. Although high workload during heart failure is associated with disruption of cardiomyocyte t-tubules and Ca homeostasis, it remains unclear whether changes in preload and afterload may promote adaptive t-tubule remodelling. We examined this issue by first investigating isolated effects of stepwise increases in load in cultured rat papillary muscles.

Combination of precipitation and size exclusion chromatography as an effective method for exosome like extracellular vesicle isolation from pericardial fluids.

Extracellular vesicles (EVs), such as exosomes, are nanovesicles that have received significant attention due to their ability to contain various molecular cargos. EVs found in biological fluids have been demonstrated to have therapeutic potential, including as biomarkers. Despite being extensively studied, a significant downfall in EV research is the lack of standardised protocol for its isolation from human biological fluids, where EVs usually exist at low densities.

Therapeutic knockdown of miR-320 improves deteriorated cardiac function in a pre-clinical model of non-ischemic diabetic heart disease.

Non-ischemic diabetic heart disease (NiDHD) is characterized by diastolic dysfunction and decreased or preserved systolic function, eventually resulting in heart failure. Accelerated apoptotic cell death because of alteration of molecular signaling pathways due to dysregulation in microRNAs (miRNAs) plays a significant role in the development of NiDHD. Here, we aimed to determine the pathological role of cardiomyocyte-enriched pro-apoptotic miR-320 in the development of NiDHD.

Cardiac Progenitor Cells and Adipocyte Stem Cells from Same Patients Exhibit In Vitro Functional Differences.

Cardiac progenitor cells (CPCs) and adipocyte stem cells (ASCs) are widely tested for their efficacy in repairing the diseased heart with varying results. However, no study has directly compared the functional efficacy of CPCs and ASCs collected from the same patient. CPCs and ASCs were isolated from the right atrial appendage and epicardial adipose tissue of the same patients, using explant culture.

Epithelial Sodium Channel δ Subunit Is Expressed in Human Arteries and Has Potential Association With Hypertension.

Background: Elevated expression and increased activity of vascular epithelial sodium channel (ENaC) can result in vascular dysfunction in small animal models. However, there is limited or no knowledge on expression and function of ENaC channels in human vasculature. Hence, this study explored the expression and function of ENaC in human arteries and their association with hypertension.

Thiamine increases resident endoglin positive cardiac progenitor cells and atrial contractile force in humans: A randomised controlled trial.

Background: The heart has an intrinsic ability to regenerate, orchestrated by progenitor or stem cells. However, the relative complexity of non-resident cardiac progenitor cell (CPC) therapy makes modulation of resident CPCs a more attractive treatment target. Thiamine analogues improve resident CPC function in pre-clinical models.

Long-chain acylcarnitine 18:1 acutely increases human atrial myocardial contractility and arrhythmia susceptibility.

Long-chain acylcarnitines (LCACs) are known to directly alter cardiac contractility and electrophysiology. However, the acute effect of LCACs on human cardiac function is unknown. We aimed to determine the effect of LCAC 18:1, which has been associated with cardiovascular disease, on the contractility and arrhythmia susceptibility of human atrial myocardium.

Human Atrial Fibrillation Is Not Associated With Remodeling of Ryanodine Receptor Clusters.

The release of Ca by ryanodine receptor (RyR2) channels is critical for cardiac function. However, abnormal RyR2 activity has been linked to the development of arrhythmias, including increased spontaneous Ca release in human atrial fibrillation (AF). Clustering properties of RyR2 have been suggested to alter the activity of the channel, with remodeling of RyR2 clusters identified in pre-clinical models of AF and heart failure.

Diabetes induces dysregulation of microRNAs associated with survival, proliferation and self-renewal in cardiac progenitor cells.

Aims/hypothesis: Diabetes mellitus causes a progressive loss of functional efficacy in stem cells, including cardiac progenitor cells (CPCs). The underlying molecular mechanism is still not known. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate genes at the post-transcriptional level.

Activation of the cardiac non-neuronal cholinergic system prevents the development of diabetes-associated cardiovascular complications.

Background: Acetylcholine (ACh) plays a crucial role in the function of the heart. Recent evidence suggests that cardiomyocytes possess a non-neuronal cholinergic system (NNCS) that comprises of choline acetyltransferase (ChAT), choline transporter 1 (CHT1), vesicular acetylcholine transporter (VAChT), acetylcholinesterase (AChE) and type-2 muscarinic ACh receptors (MAChR) to synthesize, release, degrade ACh as well as for ACh to transduce a signal. NNCS is linked to cardiac cell survival, angiogenesis and glucose metabolism.

Elevated myocardial fructose and sorbitol levels are associated with diastolic dysfunction in diabetic patients, and cardiomyocyte lipid inclusions in vitro.

Diabetes is associated with cardiac metabolic disturbances and increased heart failure risk. Plasma fructose levels are elevated in diabetic patients. A direct role for fructose involvement in diabetic heart pathology has not been investigated.

Etiology-Dependent Impairment of Diastolic Cardiomyocyte Calcium Homeostasis in Heart Failure With Preserved Ejection Fraction.

Background: Whereas heart failure with reduced ejection fraction (HFrEF) is associated with ventricular dilation and markedly reduced systolic function, heart failure with preserved ejection fraction (HFpEF) patients exhibit concentric hypertrophy and diastolic dysfunction. Impaired cardiomyocyte Ca homeostasis in HFrEF has been linked to disruption of membrane invaginations called t-tubules, but it is unknown if such changes occur in HFpEF.

Objectives: This study examined whether distinct cardiomyocyte phenotypes underlie the heart failure entities of HFrEF and HFpEF.

Combination of Cardiac Progenitor Cells From the Right Atrium and Left Ventricle Exhibits Synergistic Paracrine Effects In Vitro.

Cardiovascular diseases, such as ischemic heart disease, remain the most common cause of death worldwide. Regenerative medicine with stem cell therapy is a promising tool for cardiac repair. Combination of different cell types has been shown to improve the therapeutic potential, which is thought to be due to synergistic or complimentary reparative effects.

Inotropic and lusitropic, but not arrhythmogenic, effects of adipocytokine resistin on human atrial myocardium.

The adipocytokine resistin is released from epicardial adipose tissue (EAT). Plasma resistin and EAT deposition are independently associated with atrial fibrillation. The EAT secretome enhances arrhythmia susceptibility and inotropy of human myocardium.

Correlation between epicardial adipose tissue and body mass index in New Zealand ethnic populations.

Aim: We aimed to investigate the correlation between epicardial adipose tissue (EAT) and body mass index (BMI) in different ethnic groups in New Zealand.

Methods: The study included 205 individuals undergoing open heart surgery. Māori and Pacific groups were combined to increase statistical power.

Upregulation of microRNA-532 enhances cardiomyocyte apoptosis in the diabetic heart.

Type 2 diabetes has a strong association with the development of cardiovascular disease, which is grouped as diabetic heart disease (DHD). DHD is associated with the progressive loss of cardiovascular cells through the alteration of molecular signalling pathways associated with cell death. In this study, we sought to determine whether diabetes induces dysregulation of miR-532 and if this is associated with accentuated apoptosis.

Carvedilol and metoprolol are both able to preserve myocardial function in type 2 diabetes.

Purpose: Increasing cohorts of patients present with diabetic cardiomyopathy, and with no targeted options, treatment often rely on generic pharmaceuticals such as β-blockers. β-blocker efficacy is heterogenous, with second generation β-blocker metoprolol selectively inhibiting β -AR, while third generation β-blocker carvedilol has α -AR inhibition, antioxidant, and anti-apoptotic actions alongside nonselective β-AR inhibition. These additional properties have led to the hypothesis that carvedilol may improve cardiac contractility in the diabetic heart to a greater extent than metoprolol.

Relationship between epicardial adipose tissue thickness and epicardial adipocyte size with increasing body mass index.

Macroscopic deposition of epicardial adipose tissue (EAT) has been strongly associated with numerous indices of obesity and cardiovascular disease risk. In contrast, the morphology of EAT adipocytes has rarely been investigated. We aimed to determine whether obesity-driven adipocyte hypertrophy, which is characteristic of other visceral fat depots, is found within EAT adipocytes.

Acute interaction between human epicardial adipose tissue and human atrial myocardium induces arrhythmic susceptibility.

Epicardial adipose tissue (EAT) deposition has a strong clinical association with atrial arrhythmias; however, whether a direct functional interaction exists between EAT and the myocardium to induce atrial arrhythmias is unknown. Therefore, we aimed to determine whether human EAT can be an acute trigger for arrhythmias in human atrial myocardium. Human trabeculae were obtained from right atrial appendages of patients who have had cardiac surgery ( = 89).

Early dysregulation of cardiac-specific microRNA-208a is linked to maladaptive cardiac remodelling in diabetic myocardium.

Background: The diabetic heart undergoes remodelling contributing to an increased incidence of heart failure in individuals with diabetes at a later stage. The molecular regulators that drive this process in the diabetic heart are still unknown.

Methods: Real-time (RT) PCR analysis was performed to determine the expression of cardiac specific microRNA-208a in right atrial appendage (RAA) and left ventricular (LV) biopsy tissues collected from diabetic and non-diabetic patients undergoing coronary artery bypass graft surgery.

Diabetes induces the activation of pro-ageing miR-34a in the heart, but has differential effects on cardiomyocytes and cardiac progenitor cells.

Increased apoptosis and premature cellular ageing of the diabetic heart underpin the development of diabetic heart disease. The molecular mechanisms underlying these pathologies are still unclear. Here we determined the role of pro-senescence microRNA (miR)-34a in accelerating the ageing of the diabetic heart.