ArticleThe Journal of thoracic and cardiovascular surgery2014
Differential effects of atorvastatin on autophagy in ischemic and nonischemic myocardium in Ossabaw swine with metabolic syndrome.
Article in The Journal of thoracic and cardiovascular surgery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Efficacy and Mechanism of Preoperative Simvastatin Therapy on Myocardial Protection after Extracorporeal Circulation.BioMed research international · 2017Trial
- Association of Circulating Autophagy Proteins ATG5 and Beclin 1 with Acute Myocardial Infarction in a Case-Control Study.Cardiology · 2024Article
- Cellular Protein Quality Control in Diabetic Cardiomyopathy: From Bench to Bedside.Frontiers in cardiovascular medicine · 2020Review
- The Ossabaw Pig Is a Suitable Translational Model to Evaluate Dietary Patterns and Coronary Artery Disease Risk.The Journal of nutrition · 2018Article
- Deregulation of microRNA-193b affects the proliferation of liver cancer via myeloid cell leukemia-1.Oncology letters · 2018Article
- Resveratrol protects neuronal cells from isoflurane-induced inflammation and oxidative stress-associated death by attenuating apoptosis via Akt/p38 MAPK signaling.Experimental and therapeutic medicine · 2018Article
- Simvastatin Improves the Jaw Bone Microstructural Defect Induced by High Cholesterol Diet in Rats by Regulating Autophagic Flux.BioMed research international · 2018Article
- Hypercholesterolemia downregulates autophagy in the rat heart.Lipids in health and disease · 2017Article
- Investigating the Metabolic Syndrome: Contributions of Swine Models.Toxicologic pathology · 2016Review
- Calpain inhibition improves collateral-dependent perfusion in a hypercholesterolemic swine model of chronic myocardial ischemia.The Journal of thoracic and cardiovascular surgery · 2016Article
- Boosting autophagy in the diabetic heart: a translational perspective.Cardiovascular diagnosis and therapy · 2015Article
- Atorvastatin regulates apoptosis in chronically ischemic myocardium.Journal of cardiac surgery · 2015Article
- Intermedin attenuates myocardial infarction through activation of autophagy in a rat model of ischemic heart failure via both cAMP and MAPK/ERK1/2 pathways.International journal of clinical and experimental pathology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectivesThe 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.
methodsMale 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.
resultsIn 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.
conclusionsAtorvastatin 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.