Speaker: Professor Thomas Iskratch

Talk Title: Mechanical sensing and mechanical memory as factors in cardiovascular disease progression

Abstract:

Cardiovascular disease is a major cause of death, but is still lacking effective treatments. Mechanical properties are cues for many biological processes in health or disease, including cardiovascular pathologies. Hence, better understanding of the cardiovascular mechanosensing mechanism could result in novel therapeutic targets(1). In the heart, the extracellular matrix changes its composition and mechanical properties after myocardial infarction or due to cardiomyopathies. Cardiomyocytes, the contractile cells in the heart sense the changing mechanical properties and alter their phenotype, contributing to the disease. Similarly, vascular smooth muscle cells in the arterial wall respond to mechanical changes including extracellular matrix stiffness or heightened blood pressure, by changing the behaviour and phenotype, thereby contributing to the atherosclerotic disease progression.  

Over the past years we have focused on characterising the fundamental molecular mechanisms of the mechanosensing and signalling in both cardiomyocytes and arterial smooth muscle cells. For this we have set up and developed systems to selectively apply pathophysiological relevant forces, including stiffness, stretch, compression, or pressure. Additionally we have employed tools to measure cellular forces (nanopillar arrays, molecular tension sensors), to measure cell and tissue stiffness and micro- and nanopatterning to identify specifically the receptor sensing. By combining these tools we have started to elucidate novel cardiomyocyte specific rigidity sensing mechanisms and mechanical memory (2,3), as well as mechanosensing pathways that result in arterial smooth muscle cell phenotypic switching (4,5) that will be discussed here. 

This is a hybrid event