ArticleAmerican journal of physiology. Heart and circulatory physiology2014
Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection.
Article in American journal of physiology. Heart and circulatory physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 41 citations in OpenAlex.
- Caveolin-3: therapeutic target for diabetic myocardial ischemia/reperfusion injury.Molecular medicine (Cambridge, Mass.) · 2025Review
- Caveolin and oxidative stress in cardiac pathology.Frontiers in physiology · 2025Review
- Caveolin-3 prevents swelling-induced membrane damage via regulation of IBiophysical journal · 2022Article
- Morphine induces physiological, structural, and molecular benefits in the diabetic myocardium.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- [Significance of exosomes in cardiology: heralds of cardioprotection].Archivos de cardiologia de Mexico · 2021Review
- Dietary α-Linolenic Acid Counters Cardioprotective Dysfunction in Diabetic Mice: Unconventional PUFA Protection.Nutrients · 2020Article
- Protective role of cardiac-specific overexpression of caveolin-3 in cirrhotic cardiomyopathy.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Cardiac ischemia-reperfusion injury induces ROS-dependent loss of PKA regulatory subunit RIα.American journal of physiology. Heart and circulatory physiology · 2019Article
- Mitochondrial connexin 43 in sex-dependent myocardial responses and estrogen-mediated cardiac protection following acute ischemia/reperfusion injury.Basic research in cardiology · 2019Article
- Effects of cholesterol levels on outcomes of out-of-hospital cardiac arrest: a cross-sectional study.Clinical and experimental emergency medicine · 2019Article
- Hurdles to Cardioprotection in the Critically Ill.International journal of molecular sciences · 2019Review
- Caveolins as Regulators of Stress Adaptation.Molecular pharmacology · 2018Review
- Myocyte membrane and microdomain modifications in diabetes: determinants of ischemic tolerance and cardioprotection.Cardiovascular diabetology · 2017Review
- TIR/BB-loop mimetic AS-1 attenuates cardiac ischemia/reperfusion injury via a caveolae and caveolin-3-dependent mechanism.Scientific reports · 2017Article
- Chronic β1-adrenoceptor blockade impairs ischaemic tolerance and preconditioning in murine myocardium.European journal of pharmacology · 2016Article
- Sarcolemmal dependence of cardiac protection and stress-resistance: roles in aged or diseased hearts.British journal of pharmacology · 2016Review
- Electrophysiology and metabolism of caveolin-3-overexpressing mice.Basic research in cardiology · 2016Article
- Cholesterol Depletion Alters Cardiomyocyte Subcellular Signaling and Increases Contractility.PloS one · 2016Article
- Investigation of therapeutic potential and molecular mechanism of vitamin P and digoxin in I/R-induced myocardial infarction in rat.Naunyn-Schmiedeberg's archives of pharmacology · 2015Article
- Opioid receptors and cardioprotection - 'opioidergic conditioning' of the heart.British journal of pharmacology · 2015Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Cholesterol-rich caveolar microdomains and associated caveolins influence sarcolemmal ion channel and receptor function and protective stress signaling. However, the importance of membrane cholesterol content to cardiovascular function and myocardial responses to ischemia-reperfusion (I/R) and cardioprotective stimuli are unclear. We assessed the effects of graded cholesterol depletion with methyl-β-cyclodextrin (MβCD) and lifelong knockout (KO) or overexpression (OE) of caveolin-3 (Cav-3) on cardiac function, I/R tolerance, and opioid receptor (OR)-mediated protection. Langendorff-perfused hearts from young male C57Bl/6 mice were untreated or treated with 0.02-1.0 mM MβCD for 25 min to deplete membrane cholesterol and disrupt caveolae. Hearts were subjected to 25-min ischemia/45-min reperfusion, and the cardioprotective effects of morphine applied either acutely or chronically [sustained ligand-activated preconditioning (SLP)] were assessed. MβCD concentration dependently reduced normoxic contractile function and postischemic outcomes in association with graded (10-30%) reductions in sarcolemmal cholesterol. Cardioprotection with acute morphine was abolished with ≥20 μM MβCD, whereas SLP was more robust and only inhibited with ≥200 μM MβCD. Deletion of Cav-3 also reduced, whereas Cav-3 OE improved, myocardial I/R tolerance. Protection via SLP remained equally effective in Cav-3 KO mice and was additive with innate protection arising with Cav-3 OE. These data reveal the membrane cholesterol dependence of normoxic myocardial and coronary function, I/R tolerance, and OR-mediated cardioprotection in murine hearts (all declining with cholesterol depletion). In contrast, baseline function appears insensitive to Cav-3, whereas cardiac I/R tolerance parallels Cav-3 expression. Novel SLP appears unique, being less sensitive to cholesterol depletion than acute OR protection and arising independently of Cav-3 expression.
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Registered trials
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