Postdoc start-up grant: Investigation of disease mechanisms in pericytes during cardiac pressure-overload

Aim of the project is understanding the role of pericytes during cardiac pressure overload with the overall goal of future therapeutic utilization. Pericytes are stabilizing cells which form the capillary system together with endothelial cells. The role of pericytes in cardiac disease is almost completely unknown. Nevertheless, it was demonstrated last year that pericytes contribute to maladaptive scar formation after myocardial infarction, but the complete ablation of pericytes led to defective vascular formation, heart failure and increased mortality. Due to their critical, tightly balanced function, we believe that understanding the role of pericytes during cardiac pressure overload will enable targeted strategies for therapeutic pericyte manipulation. First, we want to investigate myocardial activation and distribution of pericytes in the murine model of transverse aortic constriction utilizing histological methods. Next, further genetic models will be used to define the role of pericytes as well as the role of fibrogenic transcription factor SOX9 in pericytes, which we recently found as pro-inflammatory and pro-fibrotic in endothelial cells. Key parameters of our analysis will be cardiac function and anatomy, but additionally we will assess regulated genes with RNA sequencing on the single-cell level. Especially by identifying pericyte–endothelial cell, pericyte–fibroblast and pericyte–immune cell interactions we aim at establishing potential therapeutically usable targets.