Abstract 13727: The Absence of C/EBP Homologous Protein Improves Left Ventricular Remodeling After a Reperfused Myocardial Infarction
Growing evidence indicates that endoplasmic reticulum (ER) stress plays a key role in the pathogenesis of various cardiovascular diseases. C/EBP homologous protein (CHOP), a transcription factor activated during ER stress, has been implicated in the induction of apoptosis in various tissues. Very little is currently known regarding the role of ER stress and CHOP in the postinfarct myocardium. However, and importantly, in our preliminary studies, genetic deletion of CHOP did not influence infarct size determined by TTC staining after a 30-min coronary occlusion/reperfusion. We then hypothesized that genetic deletion of CHOP would improve left ventricular (LV) function and structure after a reperfused myocardial infarction (MI). Age-matched male CHOP+/+ littermates (group I, n=6), and CHOP-/- (group II, n=7) mice underwent a 30-min coronary occlusion followed by reperfusion. Echocardiography was performed 4 d prior to (BSL) and at 48 h, 21 d, and 35 d after coronary occlusion/reperfusion. Mice were sacrificed after 35 d. LV ejection fraction (EF) was significantly reduced in both groups at 48 h after MI (Figure). At 35 d after MI, mice in group II exhibited improved EF compared with group I (Figure), indicating that inhibition of myocardial CHOP signaling protects against the progressive deterioration in LV function following acute ischemia/reperfusion injury. In addition, mice in group II exhibited smaller LV end-diastolic volume compared with group I, indicating a deleterious role of myocardial CHOP signaling during postinfarct remodeling of LV. We conclude that inhibition of myocardial CHOP or modulation of relevant ER stress pathways may improve LV remodeling after MI. These findings may lead to the formulation of novel therapeutic strategies to prevent the development of ischemic cardiomyopathy.
- © 2012 by American Heart Association, Inc.