Ralph Knoell

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Muscle cells respond to mechanical stretch stimuli by triggering downstream signals for myocyte growth and survival. The molecular components of the muscle stretch sensor are unknown, and their role in muscle disease is unclear. Here, we present biophysical/biochemical studies in muscle LIM protein (MLP) deficient cardiac muscle that support a selective(More)
Mechanical instability of skeletal muscle cells is the major cause of congenital muscular dystrophy. Here we show that the zebrafish lost-contact mutant, that lacks a functional integrin-linked kinase (ilk) gene, suffers from mechanical instability of skeletal muscle fibres. With genetic and morpholino knock-down experiments we demonstrate that: 1) laminin,(More)
OBJECTIVE The aim was to examine the expression of ubiquitin (Ub), 27 kDa heat shock protein (hsp27), and hsp60 mRNA in normal and briefly ischaemic and reperfused porcine myocardium: METHODS The left anterior descending coronary artery was occluded for two periods of 10 min separated by 30 min of reperfusion. After the second occlusion the myocardium was(More)
OBJECTIVE Cardiac myosin-binding protein C (cMyBP-C) gene mutations are involved in familial hypertrophic cardiomyopathy (FHC). Many of these mutations produce truncated proteins, which are unstable in the cardiac tissue of patients, suggesting that haploinsufficiency could account for the development of the phenotype. However, existing mouse models of(More)
BACKGROUND Extracellular matrix proteins, such as laminins, and endothelial cells are known to influence cardiomyocyte performance; however, the underlying molecular mechanisms remain poorly understood. METHODS AND RESULTS We used a forward genetic screen in zebrafish to identify novel genes required for myocardial function and were able to identify the(More)
OBJECTIVES We sought to explore the relationship between a Tcap gene (TCAP) abnormality and cardiomyopathy. BACKGROUND Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) cause severe heart failure and sudden death. Recent genetic investigations have revealed that mutations of genes encoding Z-disc components, including titin and muscle LIM(More)
Because cell shape and alignment, cell-matrix adhesion, and cell-cell contact can all affect growth, and because mechanical strains in vivo are multiaxial and anisotropic, we developed an in vitro system for engineering aligned, rod-shaped, neonatal cardiac myocyte cultures. Photolithographic and microfluidic techniques were used to micropattern(More)
AIMS Muscle LIM protein (MLP) null mice are often used as a model for human dilated cardiomyopathy. So far, little is known about the time course and pathomechanisms leading to the development of the adult phenotype. METHODS AND RESULTS We systematically analysed the contractile phenotype, myofilament calcium (Ca(2)(+)) responsiveness, passive myocardial(More)
OBJECTIVE Increasing evidence points to a molecular disturbance of Ca2+ homeostasis in stunned myocardium. The aim of this study was therefore to investigate the expression of mRNAs for Ca2+ binding proteins related to the sarcoplasmic reticulum in a porcine model of myocardial stunning. METHODS In 22 anaesthetised pigs, stunning was achieved by one or(More)
BACKGROUND Heart failure is associated with impaired myocardial metabolism with a shift from fatty acids to glucose use for ATP generation. We hypothesized that cardiac accumulation of toxic lipid intermediates inhibits insulin signaling in advanced heart failure and that mechanical unloading of the failing myocardium corrects impaired cardiac metabolism.(More)