Document Detail


Differential effects of atorvastatin on autophagy in ischemic and nonischemic myocardium in Ossabaw swine with metabolic syndrome.
MedLine Citation:
PMID:  25240527     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
OBJECTIVES: The perioperative administration of pleomorphic statin drugs has been implicated in improving outcomes after cardiac surgery. Adaptive autophagy is a highly conserved cellular process that allows for the elimination of dysfunctional cell components in response to stress and survival under starving conditions. We sought to investigate the effects of the statin drug atorvastatin on autophagy in ischemic and nonischemic myocardia using a clinically relevant porcine model of metabolic syndrome.
METHODS: Male Ossabaw swine were fed a regular diet (n = 8), a high-cholesterol diet (n = 8), or a high-cholesterol diet with supplemental atorvastatin (1.5 mg/kg/d) (n = 8). After 14 weeks, all animals underwent surgical placement of an ameroid constrictor to the circumflex coronary artery to induce chronic ischemia. Nonischemic and ischemic myocardia were harvested 6 months after initiation of the diet and processed for Western blotting.
RESULTS: In the nonischemic myocardium, Western blot results demonstrate that a high cholesterol diet resulted in a statistically significant decrease in autophagy as indicated by an increase in mammalian target of rapamycin and the accumulation of several essential autophagy markers, including Beclin-1, light chain 3B-I, and light chain 3B-II. Atorvastatin supplementation prevented these changes and resulted in an increase in autophagy as indicated by a decrease in autophagy flux marker P62. In the ischemic myocardium, atorvastatin had the opposite effect, with a decrease in autophagy flux as indicated by an increase in p62 and an accumulation of light chain 3B-I, light chain B-II, and lysosome-associated membrane protein 2.
CONCLUSIONS: Atorvastatin administration has differential effects on autophagy in ischemic and nonischemic myocardia. In the setting of metabolic syndrome, atorvastatin stimulates autophagy in nonischemic myocardium while partly inhibiting autophagy in ischemic myocardium. The differential regulation on autophagy may, in part, explain the cardioprotective effect of statins in both ischemic and nonischemic myocardia, and these findings may have implications in the setting of cardiac surgery.
Authors:
Ashraf A Sabe; Nassrene Y Elmadhun; Ahmed A Sadek; Louis M Chu; Cesario Bianchi; Frank W Sellke
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Publication Detail:
Type:  Journal Article     Date:  2014-08-13
Journal Detail:
Title:  The Journal of thoracic and cardiovascular surgery     Volume:  148     ISSN:  1097-685X     ISO Abbreviation:  J. Thorac. Cardiovasc. Surg.     Publication Date:  2014 Dec 
Date Detail:
Created Date:  2014-12-01     Completed Date:  -     Revised Date:  2014-12-03    
Medline Journal Info:
Nlm Unique ID:  0376343     Medline TA:  J Thorac Cardiovasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3172-8     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
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Grant Support
ID/Acronym/Agency:
R01 HL046716/HL/NHLBI NIH HHS; R01 HL069024/HL/NHLBI NIH HHS; R01 HL085647/HL/NHLBI NIH HHS; T32 HL094300/HL/NHLBI NIH HHS

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