The effect of
hypercholesterolemia on
myocardial ischemia reperfusion injury (MIRI) is in controversy and the underlying mechanism is still not well understood. In the present study, we firstly detected the effects of
hypercholesterolemia on MIRI and the role of endoplasmic reticulum (ER) stress-mediated apoptosis pathway in this process. The
infarct size was determined by TTC staining, and apoptosis was measured by the TUNEL method. The marker
proteins of ER stress response and ER stress-mediated apoptosis pathway were detected by Western blot. The results showed that high
cholesterol diet-induced
hypercholesterolemia significantly increased the
myocardial infarct size, the release of myocardium
enzyme and the ratio of apoptosis, but did not affect the recovery of cardiac function. Moreover,
hypercholesterolemia also remarkably up-regulated the expressions of ER stress markers (
glucose-regulated
protein 78 and
calreticulin) and critical molecules in ER stress-mediated apoptosis pathway (CHOP,
caspase 12, phospho-JNK). In conclusion, our study demonstrated that
hypercholesterolemia enhanced myocardial vulnerability/sensitivity to
ischemia reperfusion injury involved in aggravation the ER stress and activation of ER stress-mediated apoptosis pathway and it gave us a new insight into the underlying mechanisms associated with
hypercholesterolemia-induced exaggerated MIRI and also provided a novel target for preventing MIRI in the presence of
hypercholesterolemia.