Intracellular Angiotensin‐II Interacts With Nuclear Angiotensin Receptors in Cardiac Fibroblasts and Regulates RNA Synthesis, Cell Proliferation, and Collagen Secretion

Abstract

Fibroblast nuclei possess AT1R and AT2R binding sites that are coupled to intranuclear Ca²⁺-mobilization and NO liberation, respectively. Intracellular Ang-II signaling regulates fibroblast proliferation, collagen gene expression, and collagen secretion. Heart failure upregulates Ang-II intracrine signaling-components in atrial fibroblasts. These results show for the first time that nuclear angiotensin-II receptor activation and intracrine Ang-II signaling control fibroblast function and may have pathophysiological significance.