The presence of RAAS inside the cells, and the functional role of intracellular renin and Ang II on the regulation of cell communication and inward calcium current lead to the concept of an intracrine RAAS (11, 24, 29–32).The hypothesis outlined here is that the intracrine renin–angiotensin system activated by aldosterone (21), hyperglycemia (33, 34), or by pathological conditions like heart failure and myocardial ischemia [when a renin transcript is overexpressed (35, 36)] is part of the genetic makeup, which is known to occur during these pathological conditions. The gene discussed is AGT; the disease is heart failure.