Role of the local renin-angiotensin system in cardiac damage: a minireview focussing on transgenic animal models.
The local generation of all components of the renin-angiotensin system (RAS) in the heart has been the basis for the postulation of a tissue RAS in this organ. Since angiotensin II is involved in the induction of cardiac hypertrophy and fibrosis the local generation of this peptide may be of highest clinical importance. Several transgenic animal models have been generated to evaluate the functional importance of the cardiac RAS. We have established a new hypertensive mouse model lacking local angiotensinogen expression in the heart. In these animals, cardiac weight and collagen synthesis are increased compared to normotensive control mice but to a lesser extent than in mice with equally enhanced blood pressure but intact cardiac angiotensinogen generation. Thus, we have shown that local synthesis of this protein is involved but not essential in the development of cardiac hypertrophy and fibrosis.
Bader
Michael
M
Max-Delbrück-Center for Molecular Medicine (MDC), D-13092, Berlin-Buch, Germany. mbader@mdc-berlin.de
D000804:Angiotensin II / Q000172:deficiency / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D006332:Cardiomegaly / Q000209:etiology* / Q000503:physiopathology; D005355:Fibrosis; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D009203:Myocardial Infarction / Q000209:etiology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D051381:Rats; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000172:deficiency / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*; D013314:Stress, Mechanical; D020257:Ventricular Remodeling
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A