Transient Increase in ATR Expression at the Myocardial Infarct Site Is Associated with Early Fibrotic Remodeling in Infarcted Rat Heart.

Abstract

Myocardial infarction initiates complex remodeling processes involving the renin-angiotensin system, through activation of the angiotensin II type 1 receptor (ATR). This study correlated ATR expression with fibrosis and cardiac function in the heart and kidneys following cardiac ischemic injury in animal models. Male Sprague-Dawley rats underwent Sham surgery, Ischemia/Reperfusion (I/R, 20-min ligation) or Permanent Ligation (PL) of the left anterior descending artery. Cardiac function was assessed by echocardiography. ATR expression was measured in the heart (infarct and remote areas) and kidneys (cortex, medulla) via [Iodine]Sarcosine-Isoleucine-Angiotensin II autoradiography. Collagen deposition was evaluated through picrosirius red staining. Left ventricular (LV) ejection fraction declined in PL models but remained stable following I/R. Post-I/R, a transient increase in cardiac ATR (day-3 to week-5) correlated with an increase in collagen, whereas after PL, elevations persisted through week-12. Infarct areas consistently displayed higher ATR and collagen than remote areas. Renal ATR and collagen levels were unchanged across groups. In analyses with pooled animals, cardiac ATR expression correlated with collagen and inversely correlated with LV Fractional Shortening (LVFS), whereas LVFS inversely correlated with collagen deposition. These findings suggest that cardiac ATR levels may serve as a target of cardiac remodeling, while changes in renal ATR appear less pronounced.