Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction.

Abstract

Increasing evidence suggests that angiotensin II (AngHI) acts as a modulator for ventricular remodeling after myocardial infarction. Using competitive reverse-transcriptase polymerase chain reaction, nuclear runoff, and binding assays, we examined the regulation of AngHI type la and lb (ATla-R and ATlb-R) and type 2 receptor (AT2-R) expression in the infarcted rat heart as well as the effects of AngiH receptor antagonists. ATla-R mRNA levels were increased in the infarcted (4.2-fold) and noninfarcted portions (2.2-fold) of the myocardium 7 d after myocardial infarction as compared with those in sham-operated controls, whereas ATlb-R mRNA levels were unchanged. The amount of detectable AT2-R mRNA increased in infarcted (3.1-fold) and noninfarcted (1.9-fold) portions relative to that in the control. The transcription rates for ATla-R and AT2-R genes, determined by means of a nuclear runoff assay, were significantly increased in the infarcted heart. The Angil receptor numbers were elevated (from 12 to 35 fmol/mg protein) in the infarcted myocardium in which the increases in AT1-R and AT2-R were 3.2-and 2.3-fold, respectively, while the receptor affinity was unchanged. Therapy with AT1-R antagonist for 7 d reduced the increase in AT1-R and AT2-R expressions in the infarcted heart together with a decrease in blood pressure, whereas therapy with an AT2-R antagonist did not affect mRNA levels and blood pressure. Neither ATi-R nor AT2-R antagonists affected the infarct sizes. These results demonstrated that myocardial infarction causes an increase in the gene transcription and protein expression of cardiac ATla-R and AT2-R, whereas the ATlb-R gene is unaffected, and that therapy with an AT1-R antagonist, but not with an AT2-R antagonist, is effective in reducing the increased expression of AngII receptor subtypes induced by myocardial infarction. (J. Clin. Invest. 1995.95:46-54.)

Interferon Regulatory Factor-1 Up-regulates Angiotensin II Type 2 Receptor and Induces Apoptosis

“…The highly abundant expression of AT 2 receptor during embryonic and neonatal growth, the rapid disappearance after birth (4,6), and the up-regulation of AT 2 receptor in myocardial infarction (27), cardiac hypertrophy (28), and skin wound (29) suggest that this receptor is closely involved with growth, development, and/or differentiation. Dudley et al (14) reported that the addition of growth factors, such as basic fibroblast growth factor or serum, to quiescent R3T3 cells caused a rapid decrease in the number of surface AT 2 receptor sites.…”

Pressure Overload Induces Cardiac Hypertrophy in Angiotensin II Type 1A Receptor Knockout Mice

“…8 -10 Many studies have demonstrated that hemodynamic overload activates the tissue RAS in the heart. [11][12][13][14][15][16] mRNA and/or protein levels of renin, 11 ACE, 12,13 angiotensinogen, 5,11,14 and Ang II receptors 15,16 have been reported to be increased in hypertrophied hearts. In addition to these in vivo studies, mechanisms by which mechanical stress induces cardiomyocyte hypertrophy have also been investigated in vitro with cultured cardiac myocytes.…”

Pertussis Toxin Up-regulates Angiotensin Type 1 Receptors through Toll-like Receptor 4-mediated Rac Activation

“…For example, an increase in AT1R density has been reported in the heart after myocardial infarction (17,18) and in hearts from biopsies from patients with spontaneous intracerebral hemorrhage (19). Several cytokines, such as tumor necrosis factor (TNF)-␣ and interleukin (IL)-1␤, have been reported to up-regulate AT1R (17,20).…”