The intracellular renin-angiotensin system: implications in cardiovascular remodeling.
OBJECTIVE
The renin-angiotensin system, traditionally viewed as a circulatory system, has significantly expanded in the last two decades to include independently regulated local systems in several tissues, newly identified active products of angiotensin II, and new receptors and functions of renin-angiotensin system components. In spite of our increased understanding of the renin-angiotensin system, a role of angiotensin II in cardiac hypertrophy, through direct effects on cardiovascular tissue, is still being debated. Here, we address the cardiovascular effects of angiotensin II and the role an intracellular renin-angiotensin system might play.


RESULTS
Recent studies have shown that cardiac myocytes, fibroblasts and vascular smooth muscle cells synthesize angiotensin II intracellularly. Some conditions, such as high glucose, selectively increase intracellular generation and translocation of angiotensin II to the nucleus. Intracellular angiotensin II regulates the expression of angiotensinogen and renin, generating a feedback loop. The first reaction of intracellular angiotensin II synthesis is catalyzed by renin or cathepsin D, depending on the cell type, and chymase, not angiotensin-converting enzyme, catalyzes the second step.


CONCLUSIONS
These studies suggest that the intracellular renin-angiotensin system is an important component of the local system. Alternative mechanisms of angiotensin II synthesis and action suggest a need for novel therapeutic agents to block the intracellular renin-angiotensin system.
Kumar
Rajesh
R
Division of Molecular Cardiology, Cardiovascular Research Institute, Texas A & M Health Science Center, College of Medicine, Temple, Texas, USA.
Singh
Vivek P
VP
Baker
Kenneth M
KM
D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use; D045604:Extracellular Fluid / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction; D020257:Ventricular Remodeling / Q000187:drug effects
D002317:Cardiovascular Agents; D000804:Angiotensin II