Abstract
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 (AT 1 ) and type 2 (AT 2 ) 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. AT 2 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 AT 2 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 AT 1 and AT 2 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 AT 1 receptor protein and decrease in AT 2 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 AT 2 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.
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