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Whether organic nitrates are bioactivated to NO in cardiac muscle cells and may thus directly affect cardiac contractile function has remained an open question. Therefore, we determined the effects of the organic nitrates glyceryl trinitrate (100 mumol/L), pentaerythritol tetranitrate (10 mumol/L), and isosorbide-5-mononitrate on electrically stimulated(More)
For studies on the regulation of myocardial protein metabolism, isolated adult cardiomyocytes were introduced as an experimental model about a decade ago. When used shortly after isolation, this model represents a tool for studying the properties of normal and diseased myocardium on the cellular level. The influence of various peptide hormones,(More)
Cardiac hypertrophy as an adaptation to increased blood pressure leads to an increase in ventricular expression of transforming growth factor Cardiac hypertrophy as an adaptation to increased blood pressure leads to an increase in ventricular expression of transforming growth factor b (TGF-b), probably via the renin-angiotensin system. We studied in vivo to(More)
The proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising treatment target to lower serum cholesterol, a major risk factor of cardiovascular diseases. Gain-of-function mutations of PCSK9 are associated with hypercholesterolemia and increased risk of cardiovascular events. Conversely, loss-of-function mutations cause low-plasma(More)
Adult ventricular cardiomyocytes have been identified as target cells for parathyroid hormone (PTH) but little is known about its signal transduction in these cells. In the present study the influence of PTH on cyclic AMP accumulation and the activity of protein kinase C (PKC) in cardiomyocytes was evaluated. A mid-regional synthetic fragment of PTH,(More)
OBJECTIVE Reperfusion injury of the myocardium is characterised by development of cardiomyocyte hypercontracture. Previous studies have shown that cGMP-mediated stimuli protect against reperfusion injury, but the cellular mechanism is still unknown. METHODS To simulate ischemia/reperfusion, adult rat cardiomyocytes were incubated anoxically (pH(o) 6.4)(More)
In some models of cardiac hypertrophy, activation of activator protein 1 (AP-1) correlates with growth. However, AP-1 is also activated by stimuli not involved in cardiac growth. This raises the following questions: does AP-1 plays a causal role for cardiomyocyte growth, and is this role model or stimulus dependent? We used a single model to address these(More)
Calcitonin gene-related peptide (CGRP), a neuropeptide localized in the cardiac autonomic nervous supply, shares 46% similarity in sequence of amino acids with amylin, a peptide synthesized in pancreatic beta-cells. In the present study, the question was addressed whether these peptides could exert hypertrophic effects in cardiomyocytes isolated from the(More)
Ventricular cardiomyocytes have previously been identified as potential target cells for parathyroid hormone-related peptide (PTHrP). Synthetic PTHrP peptides exert a positive contractile effect. Because systemic PTHrP levels are normally negligible, this suggests that PTHrP is expressed in the ventricle and acts as a paracrine mediator. We investigated the(More)
In a previous publication we reported that hypertrophic responsiveness to beta-adrenoceptor stimulation can be induced in isolated cardiomyocytes when these are cultured for 6 days in presence of fetal calf serum (FCS; Pinson et al., J. Mol. Cell. Cardiol.. 25: 477-490, 1993). The role of transforming growth factor-beta (TGF-beta) in this induction process(More)