Epicardial adipose tissue and muscle distribution affect outcomes in very old patients after transcatheter aortic valve replacement.

Aims: To analyse the relevance of body composition and blood markers for long-term outcomes in very old patients after transcatheter aortic valve replacement (TAVR).

Methods And Results: A total of 403 very old patients were characterized with regard to subcutaneous, visceral, and epicardial fat, psoas muscle area, plasma growth differentiation factor 15 (GDF-15), and leptin. Cohorts grouped by body mass index (BMI) were analysed for long-term outcomes.

A common gene signature of the right ventricle in failing rat and human hearts.

The molecular mechanisms of progressive right heart failure are incompletely understood. In this study, we systematically examined transcriptomic changes occurring over months in isolated cardiomyocytes or whole heart tissues from failing right and left ventricles in rat models of pulmonary artery banding (PAB) or aortic banding (AOB). Detailed bioinformatics analyses resulted in the identification of gene signature, protein and transcription factor networks specific to ventricles and compensated or decompensated disease states.

Inhibition of MMP2 activity mitigates N-omega-nitro-l-arginine-methyl ester (l-NAME)-induced right heart failure.

In rats decreased bioavailability of nitric oxide induces oxidative stress and right heart failure. Oxidative stress can activate matrix metalloproteinase-2 (MMP2). We addressed the question whether increasing oxidative defense by administration of the SOD mimetic Tempol or direct inhibition of MMP2 activity by SB-3CT mitigates right heart failure.

CTRP13-Mediated Effects on Endothelial Cell Function and Their Potential Role in Obesity.

Background: Obesity, a major component of cardiometabolic syndrome, contributes to the imbalance between pro- and anti-atherosclerotic factors via dysregulation of adipocytokine secretion. Among these adipocytokines, the C1q/TNF-related proteins (CTRPs) play a role in the modulation of atherosclerosis development and progression. Here, we investigated the vascular effects of CTRP13.

Comparison of the stage-dependent mitochondrial changes in response to pressure overload between the diseased right and left ventricle in the rat.

The right ventricle (RV) differs developmentally, anatomically and functionally from the left ventricle (LV). Therefore, characteristics of LV adaptation to chronic pressure overload cannot easily be extrapolated to the RV. Mitochondrial abnormalities are considered a crucial contributor in heart failure (HF), but have never been compared directly between RV and LV tissues and cardiomyocytes.

The ratio of cytochrome c oxidase subunit 4 isoform 4I1 and 4I2 mRNA is changed in permanent atrial fibrillation.

Aims: The conditions of hypoxia are suggested to induce permanent atrial fibrillation (AF). The regulation of COX4I2 and COX4I1 depends on oxygen availability in tissues. A role of COX4I2 in the myocardium of AF patients is supposed for pathogenesis of AF and subsequent alterations in the electron transfer chain (ETC) under hypoxia.

Calcium Handling Remodeling Underlies Impaired Sympathetic Stress Response in Ventricular Myocardium from Haploinsufficient Rats.

encodes the pore-forming α1C subunit of the L-type Ca channel, Cav1.2. Mutations and polymorphisms of the gene are associated with neuropsychiatric and cardiac disease.

Monoamine Oxidase A Contributes to Serotonin-But Not Norepinephrine-Dependent Damage of Rat Ventricular Myocytes.

Serotonin effects on cardiac hypertrophy, senescence, and failure are dependent either on activation of specific receptors or serotonin uptake and serotonin degradation by monoamine oxidases (MAOs). Receptor-dependent effects are specific for serotonin, but MAO-dependent effects are nonspecific as MAOs also metabolize other substrates such as catecholamines. Our study evaluates the role of MAO-A in serotonin- and norepinephrine-dependent cell damage.

Effect of Anti-Hypertensive Medication on Plasma Concentrations of Lysyl Oxidase: Evidence for Aldosterone-IL-6-Dependent Regulation of Lysyl Oxidase Blood Concentration.

Lysyl oxidase (LOX) is a secretory protein that catalyzes elastin and collagen cross-linking. Lowering LOX expression and activity in endothelial cells is associated with a high risk of aneurysms and vascular malformation. Interleukin-6 (IL-6), elevated in hypertension, is known to suppress LOX expression.

Rationale and Initiative of the Impella in Cardiac Surgery (ImCarS) Register Platform.

Objectives: Cardiac support systems are being used increasingly more due to the growing prevalence of heart failure and cardiogenic shock. Reducing cardiac afterload, intracardiac pressure, and flow support are important factors. Extracorporeal membrane oxygenation (ECMO) and intracardiac microaxial pump systems (Impella) as non-permanent MCS (mechanical circulatory support) are being used increasingly.

AMPK Activation Is Indispensable for the Protective Effects of Caloric Restriction on Left Ventricular Function in Postinfarct Myocardium.

Background: Caloric restriction (CR) extends lifespan in many species, including mammals. CR is cardioprotective in senescent myocardium by correcting pre-existing mitochondrial dysfunction and apoptotic activation. Furthermore, it confers cardioprotection against acute ischemia-reperfusion injury.

Surgical Ablation of Permanent Atrial Fibrillation: Age, LV Dilatation, Obesity.

Objectives: Although concomitant surgical ablation can help to reach freedom from atrial fibrillation (FREEAF) even in patients with permanent atrial fibrillation (AF), some cardiac surgeons hesitate to perform concomitant ablation to avoid perioperative risk escalation. Here, we investigated outcome and predicators of therapeutic success of concomitant surgical ablation in an all-comers study.

Methods: Ablation-naïve patients with formerly accepted permanent AF (FAP,  = 41) or paroxysmal AF (parAF,  = 24) underwent concomitant epicardial bipolar radio frequency ablation and implantable loop recorder (ILR) at two surgical departments.

Comparative Analysis of CTRP-Mediated Effects on Cardiomyocyte Glucose Metabolism: Cross Talk between AMPK and Akt Signaling Pathway.

C1q/tumor necrosis factor -alpha-related proteins (CTRPs) have been shown to mediate protective cardiovascular effects, but no data exists on their effects on glucose and fatty acid (FA) metabolism in cardiomyocytes. In the present study, adult rat cardiomyocytes and H9C2 cardiomyoblasts were stimulated with various recombinant CTRPs. Glucose or FA uptake, expression of genes involved in glucose or FA metabolism and the role of the AMP-activated protein kinase (AMPK) and Akt were investigated.

Impact of PCSK9 on CTRP9-Induced Metabolic Effects in Adult Rat Cardiomyocytes.

The adipocytokine adiponectin and its structural homologs, the C1q/TNF-related proteins (CTRPs), increase insulin sensitivity, fatty acid oxidation and mitochondrial biogenesis. Adiponectin- and CTRP-induced signal transduction has been described to involve the adiponectin receptors and a number of co-receptors including the Low density lipoprotein receptor-related protein 1 (LRP1). LRP1 is another target of the proprotein convertase subtilisin/kexin-9 (PCSK9) in addition to the LDL-receptor (LDL-R).

Importance of Cx43 for Right Ventricular Function.

In the heart, connexins form gap junctions, hemichannels, and are also present within mitochondria, with connexin 43 (Cx43) being the most prominent connexin in the ventricles. Whereas the role of Cx43 is well established for the healthy and diseased left ventricle, less is known about the importance of Cx43 for the development of right ventricular (RV) dysfunction. The present article focusses on the importance of Cx43 for the developing heart.

Caloric restriction reduces sympathetic activity similar to beta-blockers but conveys additional mitochondrio-protective effects in aged myocardium.

Increased activation of sympathetic nervous system contributes to congestive heart failure (CHF) progression, and inhibition of sympathetic overactivation by beta-blockers is successful in CHF patients. Similarly, caloric restriction (CR) reduces sympathetic activity but mediates additional effects. Here, we compared the cardiac effects of CR (- 40% kcal, 3 months) with beta-blocker therapy (BB), diuretic medication (DF) or control diet in 18-months-old Wistar rats.

Autocrine effects of PCSK9 on cardiomyocytes.

Proprotein convertase subtilisin kexin type 9 (PCSK9) is in the focus of cardiovascular research due to its role in hepatic low density lipoprotein (LDL) clearance. However, extrahepatic expression of PCSK9 such as in cardiomyocytes and its regulation by oxidized LDL (oxLDL) put notion on extrahepatic effects of PCSK9 as well. This study was aimed to reveal the role of PCSK9 in oxLDL-dependent regulation of cardiomyocyte function.

Effects of air pollution particles (ultrafine and fine particulate matter) on mitochondrial function and oxidative stress - Implications for cardiovascular and neurodegenerative diseases.

Environmental pollution is a major cause of global mortality and burden of disease. All chemical pollution forms together may be responsible for up to 12 million annual excess deaths as estimated by the Lancet Commission on pollution and health as well as the World Health Organization. Ambient air pollution by particulate matter (PM) and ozone was found to be associated with an all-cause mortality rate of up to 9 million in the year 2015, with the majority being of cerebro- and cardiovascular nature (e.

Differential effects of right and left heart failure on skeletal muscle in rats.

Background: Exercise intolerance is a cardinal symptom in right (RV) and left ventricular (LV) failure. The underlying skeletal muscle contributes to increased morbidity in patients. Here, we compared skeletal muscle sarcopenia in a novel two-stage model of RV failure to an established model of LV failure.

Effect of p53 activation on experimental right ventricular hypertrophy.

The leading cause of death in Pulmonary Arterial Hypertension (PAH) is right ventricular (RV) failure. The tumor suppressor p53 has been associated with left ventricular hypertrophy (LVH) and remodeling but its role in RV hypertrophy (RVH) is unclear. The purpose of this study was to determine whether pharmacological activation of p53 by Quinacrine affects RV remodeling and function in the pulmonary artery banding (PAB) model of compensated RVH in mice.

CTRP9 Mediates Protective Effects in Cardiomyocytes via AMPK- and Adiponectin Receptor-Mediated Induction of Anti-Oxidant Response.

The C1q/tumor necrosis factor-alpha-related protein 9 (CTRP9) has been reported to exert cardioprotective effects, but its role in the right ventricle (RV) remains unclear. To investigate the role of CTRP9 in RV hypertrophy and failure, we performed pulmonary artery banding in weanling rats to induce compensatory RV hypertrophy seven weeks after surgery and RV failure 22 weeks after surgery. CTRP9 expression, signal transduction and mechanisms involved in protective CTRP9 effects were analyzed in rat and human RV tissue and cardiac cells.

Alterations in Glucose Metabolism During the Transition to Heart Failure: The Contribution of UCP-2.

The cardiac expression of the mitochondrial uncoupling protein (UCP)-2 is increased in patients with heart failure. However, the underlying causes as well as the possible consequences of these alterations during the transition from hypertrophy to heart failure are still unclear. To investigate the role of UCP-2 mechanistically, expression of UCP-2 was silenced by small interfering RNA in adult rat ventricular cardiomyocytes.

SIAH2-mediated and organ-specific restriction of HO-1 expression by a dual mechanism.

The intracellular levels of the cytoprotective enzyme heme oxygenase-1 (HO-1) are tightly controlled. Here, we reveal a novel mechanism preventing the exaggerated expression of HO-1. The analysis of mice with a knock-out in the ubiquitin E3 ligase seven in absentia homolog 2 (SIAH2) showed elevated HO-1 protein levels in specific organs such as heart, kidney and skeletal muscle.

Inhibition of Protein Prenylation of GTPases Alters Endothelial Barrier Function.

The members of Rho family of GTPases, RhoA and Rac1 regulate endothelial cytoskeleton dynamics and hence barrier integrity. The spatial activities of these GTPases are regulated by post-translational prenylation. In the present study, we investigated the effect of prenylation inhibition on the endothelial cytoskeleton and barrier properties.