Transient Increase in AT₁R Expression at the Myocardial Infarct Site Is Associated with Early Fibrotic Remodeling in...

Myocardial infarction initiates complex remodeling processes involving the renin-angiotensin system, through activation of the angiotensin II type 1 receptor (AT₁R). This study correlated AT₁R 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. AT₁R expression was measured in the heart (infarct and remote areas) and kidneys (cortex, medulla) via [¹²⁵Iodine]Sarcosine¹-Isoleucine⁸-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 AT₁R (day-3 to week-5) correlated with an increase in collagen, whereas after PL, elevations persisted through week-12. Infarct areas consistently displayed higher AT₁R and collagen than remote areas. Renal AT₁R and collagen levels were unchanged across groups. In analyses with pooled animals, cardiac AT₁R expression correlated with collagen and inversely correlated with LV Fractional Shortening (LVFS), whereas LVFS inversely correlated with collagen deposition. These findings suggest that cardiac AT₁R levels may serve as a target of cardiac remodeling, while changes in renal AT₁R appear less pronounced.