Abstract 15393: Peroxisome Proliferator Activated Receptor Gamma Coactivator-1alpha Regulates Cardiomyocyte Oxidative Stress Responsiveness in ST-segment Elevation Acute Myocardial Infarction
Background: Peroxisome Proliferator Activated Receptor Gamma Coactivator-1alpha (PGC-1α), a master transcription factor that regulates oxidative stress mitochondrial protection system, is induced on ischemia-reperfusion injury. The aim of the study was to evaluate the role of PGC-1α in the myocardial protection after acute coronary syndromes
Methods: We included 51 patients with ST-segment elevation myocardial infarction (STEMI) who received reperfusion therapy. RNA was isolated from blood samples obtained at admission and after 72 hours. PGC-1α and different mitochondrial protection system targets expression were determinated by PCR. Patients were divided in two groups depending on the induction of PGC-1α. Myocardial infarction size was compared between the groups analyzing cardiac biomarkers maximum levels, left ventricular ejection fraction (LVEF) and segmental wall motion abnormalities (SWMA), and the percentage of necrotic area estimated by late gadolinium enhancement in magnetic resonance imaging.
Results: Patients with higher induction of the PGC-1α expression after STEMI presented bigger myocardial infarctions (% of necrotic area: 24,91 vs 10,72; p=0,041), higher troponin peak (TnI: 119,87 vs 61,88 mg/dL; p=0,031) and lower LVEF (47,41 vs 53,75 %; p=0,027) and higher SWMA score (1,79 vs 1,38; p=0,041) measured by echocardiography. Induction of PGC-1α was correlated with higher expression of mitochondrial protection targets: manganese superoxide dismutase (MnSOD) and glutathione peroxidase 3 (Gpx3).
Conclusions: PGC-1α participates in the mitochondrial responsiveness initiated in the myocardium after STEMI, increasing expression of oxidative stress system targets. Its induction that can be measured in blood samples is higher in more extensive infarctions. PGC-1α can play a determinant role activating ischemia-reperfusion injury molecular targets and so regulating the apoptosis inhibition of the cardiomyocytes at risk.
- © 2011 by American Heart Association, Inc.