THE ROLE OF THE FIBROBLAST IN STRUCTURING THE CARDIAC MICROENVIRONMENT

Abstract

Fibroblasts are important non-muscle cells in the heart. Their contribution to cardiac development, physiology, and pathology is evident. The primary physiological role of the cardiac fibroblast is the production of extracellular matrix (ECM) network that determines cardiac stiffness and structure and also coordinates extracellular signaling. In addition to their critical role in ECM synthesis, fibroblasts produce cytokines and proteases that directly affect ECM organization and turnover, and influence neonatal cardiomyocyte proliferation. Our knowledge of fibroblast biology is based largely on in vitro studies that cannot recapitulate the complex cellular and biophysical milieu of the working heart. In my dissertation work, I have investigated the role of fibroblasts in the perinatal and adult heart using transgenic deletion of these cells. My overall hypothesis is that ECM deposition and organization by cardiac fibroblasts are required for normal heart development and homeostatic maintenance, and that perturbation of these cells leads to accelerated heart dysfunction after injury.