Up-regulated expression of angiotensin II type 1 receptor gene in human pathologic hearts.
BACKGROUND
An accumulation of evidence suggests that the local renin-angiotensin system plays a role in the development of cardiac hypertrophy in vivo; however, it remains unknown how the expression of angiotensin II type 1 receptor (AT1), which mediates most of the cardiovascular effects of angiotensin II, is regulated in the left ventricles of human pathologic hearts.


RESULTS
Expression of AT1 gene in the left ventricle wall of 14 autopsied human hearts was examined by reverse transcription polymerase chain reaction. The levels of AT1 messenger RNA relative to those of beta-actin messenger RNA in the left ventricle wall were increased 3.8-fold in the hearts with dilated cardiomyopathy (n = 4, P < .05) and 6.2-fold in the noninfarcted areas of hearts with old myocardial infarction (n = 4, P < .05), compared with the control hearts without any cardiac disease (n = 6). The increases in the relative AT1 messenger RNA level showed a positive correlation with myocyte diameter in the adjacent tissue (r = .927, P < .001 for dilated cardiomyopathy and r = .934, P < .005 for old myocardial infarctions) and with the extent of fibrosis (r = .880, P < .005 for dilated cardiomyopathy and r = .690, P < .05 for old myocardial infarction).


CONCLUSIONS
Expression of AT1 in these human pathologic hearts was associated with myocardial cell hypertrophy and extent of fibrosis, a finding that further emphasizes the importance of the local renin-angiotensin system in the remodeling of human hearts with dilated cardiomyopathy and old myocardial infarction.
Ohtani
S
S
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan.
Fujiwara
H
H
Hasegawa
K
K
Doyama
K
K
Inada
T
T
Tanaka
M
M
Fujiwara
T
T
Sasayama
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001345:Autoradiography; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011945:Receptors, Angiotensin / Q000235:genetics*; D015854:Up-Regulation
D012333:RNA, Messenger; D011945:Receptors, Angiotensin