Background: Glucagon-like peptide-1 (GLP-1) is a gut-derived peptide secreted in response to nutritional and inflammatory stimuli. Elevated GLP-1 levels predict adverse outcome in patients with acute myocardial infarction or sepsis. GLP-1 holds cardioprotective effects and GLP-1 receptor agonists reduce cardiovascular events in high-risk patients with diabetes.
View Article and Find Full Text PDFPatients with advanced chronic kidney disease (CKD) mostly die from sudden cardiac death and recurrent heart failure. The mechanisms of cardiac remodeling are largely unclear. To dissect molecular and cellular mechanisms of cardiac remodeling in CKD in an unbiased fashion, we performed left ventricular single-nuclear RNA sequencing in two mouse models of CKD.
View Article and Find Full Text PDFAim: Chronic kidney disease (CKD) is accompanied by increased cardiovascular risk and heart failure (HF). In rodents, 2,8-dihydroxyadenine (DHA)-induced nephropathy is a frequently used CKD model. Cardiac and kidney tubular cells share high energy demand to guarantee constant contractive force of the heart or reabsorption/secretion of primary filtrated molecules and waste products by the kidney.
View Article and Find Full Text PDFIntroduction: Intensive care unit (ICU) structural and spatial design may play a role in infection prevention and control.
Methods: Between 09/2021 and 11/2021 we performed an online survey among ICUs in Germany, Austria and Switzerland.
Results: A total of 597 (40%) of the invited ICUs answered the survey; 20% of the ICUs were built before 1990.
Aims: Patients with chronic kidney disease (CKD) have an increased risk of cardiovascular events and exhibit myocardial changes including left ventricular (LV) hypertrophy and fibrosis, overall referred to as 'uremic cardiomyopathy'. Although different CKD animal models have been studied for cardiac effects, lack of consistent reporting on cardiac function and pathology complicates clear comparison of these models. Therefore, this study aimed at a systematic and comprehensive comparison of cardiac function and cardiac pathophysiological characteristics in eight different CKD models and mouse strains, with a main focus on adenine-induced CKD.
View Article and Find Full Text PDFPatients with diabetes have a high cardiovascular risk, which can be efficiently addressed by the administration of glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1-RA). Nevertheless, the use of GLP-1-RA has so far been limited in cardiology. This review describes the existing evidence for cardiovascular benefits of GLP-1-RA and presents the available substances with recommendations on administration and titration and taking the side effects into consideration.
View Article and Find Full Text PDFAim: To investigate cardiac signalling pathways connecting substrate utilization with left ventricular remodelling in a murine pressure overload model.
Methods: Cardiac hypertrophy was induced by transverse aortic constriction surgery in 20-week-old C57BL/6J mice treated with or without the sodium-glucose co-transporter 2 (SGLT2) inhibitor ertugliflozin (225 mg kg chow diet) for 10 weeks.
Results: Ertugliflozin improved left ventricular function and reduced myocardial fibrosis.
The cardiac vascular and perivascular niche are of major importance in homeostasis and during disease, but we lack a complete understanding of its cellular heterogeneity and alteration in response to injury as a major driver of heart failure. Using combined genetic fate tracing with confocal imaging and single-cell RNA sequencing of this niche in homeostasis and during heart failure, we unravel cell type specific transcriptomic changes in fibroblast, endothelial, pericyte and vascular smooth muscle cell subtypes. We characterize a specific fibroblast subpopulation that exists during homeostasis, acquires Thbs4 expression and expands after injury driving cardiac fibrosis, and identify the transcription factor TEAD1 as a regulator of fibroblast activation.
View Article and Find Full Text PDFGlucose and its metabolites provide building blocks for cellular structures and modifications occurring on proteins, lipids and nucleotides. The underlying reactions consist of glycosylations controlled by hundreds of enzymes following a specific yet incompletely understood architecture of cell physiology and glycations as random, not controlled modifications occurring in an oxidative environment. In both cases attachments of glucose or its metabolites can modulate the tertiary structure of proteins as required for cellular physiology or cause disturbance with disease driving pathology.
View Article and Find Full Text PDFBackground: In patients with chronic kidney disease (CKD), atrial fibrillation (AF) is highly prevalent and represents a major risk factor for stroke and death. CKD is associated with atrial proarrhythmic remodeling and activation of the sympathetic nervous system. Whether reduction of the sympathetic nerve activity by renal denervation (RDN) inhibits AF vulnerability in CKD is unknown.
View Article and Find Full Text PDFBackground: The gut incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) are secreted by enteroendocrine cells following food intake leading to insulin secretion and glucose lowering. Beyond its metabolic function GIP has been found to exhibit direct cardio- and atheroprotective effects in mice and to be associated with cardiovascular prognosis in patients with myocardial infarction. The aim of this study was to characterize endogenous GIP levels in patients with acute myocardial infarction.
View Article and Find Full Text PDFChronic kidney disease (CKD) triggers the risk of developing uremic cardiomyopathy as characterized by cardiac hypertrophy, fibrosis and functional impairment. Traditionally, animal studies are used to reveal the underlying pathological mechanism, although variable CKD models, mouse strains and readouts may reveal diverse results. Here, we systematically reviewed 88 studies and performed meta-analyses of 52 to support finding suitable animal models for future experimental studies on pathological kidney-heart crosstalk during uremic cardiomyopathy.
View Article and Find Full Text PDFAims: Recent studies have found circulating concentrations of the gastrointestinal hormone GLP-1 to be an excellent predictor of cardiovascular risk in patients with myocardial infarction. This illustrates a yet not appreciated crosstalk between the gastrointestinal and cardiovascular systems, which requires further investigation. The gut-derived hormone Peptide YY (PYY) is secreted from the same intestinal L-cells as GLP-1.
View Article and Find Full Text PDFBackground: Nephropathologic analyses provide important outcomes-related data in experiments with the animal models that are essential for understanding kidney disease pathophysiology. Precision medicine increases the demand for quantitative, unbiased, reproducible, and efficient histopathologic analyses, which will require novel high-throughput tools. A deep learning technique, the convolutional neural network, is increasingly applied in pathology because of its high performance in tasks like histology segmentation.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
August 2020
Objectives: Investigation of the effect of SGLT2 inhibition by empagliflozin on left ventricular function in a model of diabetic cardiomyopathy.
Background: SGLT2 inhibition is a new strategy to treat diabetes. In the EMPA-REG Outcome trial empagliflozin treatment reduced cardiovascular and overall mortality in patients with diabetes presumably due to beneficial cardiac effects, leading to reduced heart failure hospitalization.
SGLT-2 inhibitors and most GLP-1 receptor agonists demonstrated cardiovascular superiority and reduction of cardiovascular and overall mortality. These results stand as a turning point in the management of diabetes, shifting the focus from controlling glucose levels to mastering the extra-glycemic effects of these new drugs. This narrative review will discuss recent CVOT with focus on SGLT-2 inhibitors and GLP-1 receptor agonists to distinguish relevant patients' characteristics as potential predictors for therapeutic efficacy.
View Article and Find Full Text PDFAims: Glucagon-like peptide 1 (GLP-1) is a gut incretin hormone inducing post-prandial insulin secretion. Glucagon-like peptide 1 levels were recently found to be increased in patients with acute myocardial infarction. Glucagon-like peptide 1 receptor agonists improve cardiovascular outcomes in patients with diabetes.
View Article and Find Full Text PDFIncretin-based therapies, including glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors, are potent glucose-lowering drugs. Still, only GLP-1 receptor agonists with close peptide homology to GLP-1 (liraglutide and semaglutide) but neither exenatide-based GLP-1 receptor agonists nor DPP-4 inhibitors were found to reduce cardiovascular events. This different response might relate to GLP-1 receptor-independent actions of GLP-1 caused by cleavage products only liberated by GLP-1 receptor agonists with close peptide structure to GLP-1.
View Article and Find Full Text PDFCardiac surgery with cardiopulmonary bypass (CPB) triggers myocardial ischemia/reperfusion injury contributing to organ dysfunction. Preclinical studies revealed that dipeptidyl peptidase (DPP4) inhibition is protective during myocardial infarction. Here, we assessed for the first time the relation of peri-operative DPP4-activity in serum of 46 patients undergoing cardiac surgery with patients' post-operative organ dysfunction during intensive care unit (ICU) stay.
View Article and Find Full Text PDFMyocardial infarction causes rapid impairment of left ventricular function and requires a hypercontractile response of non-infarcted tissue areas to maintain haemodynamic stability. This compensatory adaptation is mediated by humoral, inflammatory and neuronal signals. GLP-1 is an incretin hormone with glucoregulatory and cardioprotective capacities and is secreted in response to nutritional and inflammatory stimuli.
View Article and Find Full Text PDFOxidized low-density lipoprotein (oxLDL) and associated oxidized phosphocholine-headgroup phospholipids (oxPCs) activate blood platelets through ligation of the scavenger receptor CD36. Previously, we found that oxLDL stimulated phosphorylation of phospholipase Cγ2 (PLCγ2). However, the functional relevance of PLCγ2 phosphorylation in oxLDL-mediated platelet hyperactivity remained elusive.
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