Atorvastatin Regulates Apoptosis in Chronically Ischemic Myocardium

作者：Sabe Ashraf A; Elmadhun Nassrene Y; Sadek Ahmed A; Dalal Rahul S; Chu Louis M; Bianchi Cesario; Sellke Frank W^*

来源：Journal of Cardiac Surgery, 2015, 30(2): 218-223.

DOI：10.1111/jocs.12488

BackgroundWe previously demonstrated that atorvastatin upregulates proangiogenic proteins and increases arteriolar density in ischemic myocardium. Despite this, there was a lack of collateral-dependent perfusion, possibly related to apoptosis. We utilized a swine model of metabolic syndrome and chronic myocardial ischemia to investigate the effects of atorvastatin on apoptosis.
Materials and methodsSixteen Ossabaw miniswine were fed a high-cholesterol diet for 14 weeks then underwent surgical placement of an ameroid constrictor to their circumflex artery inducing chronic ischemia. Eight pigs additionally received supplemental atorvastatin (1.5mg/kg daily). Myocardium was harvested six months later for western blotting and TUNEL staining.
ResultsAnimals supplemented with atorvastatin had significant increases in markers associated with apoptosis including p-38, BAX, and caspase 3 (p<0.05). Atorvastatin supplementation also resulted in significant increases in expression of cell survival proteins Bcl-2 and P-ERK and an overall decrease in apoptosis demonstrated by TUNEL staining (p<0.05).
ConclusionsAtorvastatin acts on multiple pathways and its effects on angiogenesis remain unclear. Although there is increased expression in several markers of apoptosis, key anti-apoptotic proteins were also upregulated with an overall decrease in apoptosis. Further investigation of these pathways may provide insight into the role of statins on myocardial protection after ischemia. doi: 10.1111/jocs.12488 (J Card Surg 2015;30:218-223)

• 出版日期2015-2