Abstract 5422: Effect of Age on Expression of AT1 and AT2 Receptors and ACE-2, Angiotensin (1–7), Ac-SDKP and Smad-2 Proteins After Acute Reperfused ST-Segment Elevation Myocardial Infarction
Recent evidence suggests that aging alters the expression of inflammatory cytokines, impairs healing and promotes adverse left ventricular (LV) remodeling after chronic reperfused ST-segment elevation myocardial infarction (RSTEMI). Whether aging alters the expression of angiotensin II type 1 (AT1) and type 2 (AT2) receptors, and angiotensin-converting-enzyme-2 (ACE-2), angiotensin (Ang) (1–7), N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) and Smad-2 proteins early after acute RSTEMI is not known. AT2 receptors have been implicated in cardioprotection, ACE-2 and Ang (1–7) in the counter-regulatory arm of the renin-angiotensin-system (RAS) and Ac-SDKP in inflammation and collagen synthesis. We hypothesized that aging is associated with downregulation of AT2 receptors and ACE-2, Ang (1–7), Ac-SDKP and Smad-2 proteins. We compared in-vivo LV remodeling and function (echocardiography/Doppler) and the ex-vivo molecular expression of AT1 and AT2 receptors, ACE-2, Ang (1–7) and Ac-SDKP after acute RSTEMI (90 min no-flow ischemia and 120 min reperfusion) in young (group 1, n=12) and old (group 2, n=12) dogs. Compared to group 1 controls, group 2 hearts showed more severe echocardiographic LV remodeling and dysfunction (with lower ejection fraction, larger volumes and more diastolic dysfunction, infarct expansion and thinning). In addition, group 2 hearts showed no change in AT1 receptor protein and decrease in AT2 receptor protein and ACE-2, Ang (1–7), Ac-SDKP and Smad-2 proteins in the reperfused ischemic zone. The findings suggest that aging is associated with changes in proteins in the regulatory as well as the counter-regulatory arm of the RAS during acute RSTEMI. The age-related downregulation of AT2 receptors, ACE-2, Ang (1–7), Ac-SDKP and Smad-2 may contribute to the more severe LV remodeling and dysfunction after acute RSTEMI. Targeting these proteins early during reperfusion may improve outcome in acute RSTEMI.