Crosstalk between the renin-angiotensin system and the advance glycation end product axis in the heart: role of the cardiac fibroblast.

Cardiac fibroblasts (CFs) are involved in maintaining extracellular matrix (ECM) homeostasis in the heart. CFs mediate responses to hormonal and mechanical stimuli and relay these to other local cell types through release of autocrine and/or paracrine factors. CFs also play important roles in the setting of injury, i.e., myocardial infarction, where ECM production is key to efficient scarring. However, conditions exist in which excess production of ECM by CFs can lead to cardiac fibrosis. Two important pathways known to be involved in development of cardiac fibrosis are renin-angiotensin system (RAS) and advanced glycation end products (AGE) receptor (RAGE) signaling cascades. This report summarizes actions of these two pathways on function of CFs. Because cardiac fibrosis is an important component of diabetic cardiomyopathy, we include new data that suggests a possible crosstalk between the RAS and AGE/RAGE pathway in order to activate CFs in diabetes.