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Atorvastatin Regulates Apoptosis in Chronically Ischemic Myocardium
Author(s) -
Sabe Ashraf A.,
Elmadhun Nassrene Y.,
Sadek Ahmed A.,
Dalal Rahul S.,
Chu Louis M.,
Bianchi Cesario,
Sellke Frank W.
Publication year - 2015
Publication title -
journal of cardiac surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.428
H-Index - 58
eISSN - 1540-8191
pISSN - 0886-0440
DOI - 10.1111/jocs.12488
Subject(s) - atorvastatin , medicine , tunel assay , apoptosis , ischemia , downregulation and upregulation , angiogenesis , statin , pharmacology , cardiology , endocrinology , immunohistochemistry , biology , biochemistry , gene
Background We 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 methods Sixteen 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 (1.5 mg/kg daily). Myocardium was harvested six months later for western blotting and TUNEL staining. Results Animals 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). Conclusions Atorvastatin 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)