Excessive hypertension and end-organ damage in a transgenic mouse line carrying the rat angiotensinogen gene.
The renin-angiotensin system plays an important role in the etiology of cardiovascular diseases. Three transgenic mouse lines overexpressing rat angiotensinogen (rAOGEN) were generated. The aim of our study was to characterize the originally undescribed second transgenic line TGM(rAOGEN)102. The transgene tissue distribution and expression of brain natriuretic peptide and collagen type III were investigated by ribonuclease protection assay. Catheter measurements of blood pressure and cardiac function were performed in anesthetized mice. End-organ fibrosis was further assessed by van Gieson staining. In line TGM(rAOGEN)102, the rAOGEN transgene was mainly expressed in liver and brain but could also be detected in hearts, kidneys, and lungs. Transgenic mice developed excessive chronic hypertension compared with their wild-type littermates. The rise of blood pressure was paralleled by cardiac hypertrophy, impaired cardiac function, and increased expression of brain natriuretic peptide. Pronounced fibrosis was detected in the hearts, lungs, and kidneys of transgenic mice. Our data indicate that overexpression of rAOGEN in mice leads to excessive hypertension, cardiac hypertrophy, impaired heart function, and pronounced fibrosis. Thus, this line TGM(rAOGEN)102 provides a new model to study hypertension-mediated end-organ damage and to evaluate new antihypertensive or cardioprotective drugs.
Xu
Ping
P
Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Wang
Yong
Y
Sterner-Kock
Anja
A
Bader
Michael
M
Schultheiss
Heinz-Peter
HP
Walther
Thomas
T
D000808:Angiotensinogen / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D005796:Genes; D006321:Heart / Q000503:physiopathology; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D055647:Rats, Transgenic; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology
D000959:Antihypertensive Agents; D000808:Angiotensinogen