Effect of statins on mitochondrial function and contractile force in human skeletal and cardiac muscle

• Published in: Biomedicine & pharmacotherapy Vol. 180; p. 117492
• Main Authors: Somers, Tim, Siddiqi, Sailay, Janssen, Margit C.M., Morshuis, Wim J., Maas, Renee G.C., Buikema, Jan W., van den Broek, Petra H.H., Schirris, Tom J.J., Russel, Frans G.M.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.11.2024; Elsevier
• Subjects: Aged; Cardiac muscle; Cellular respiration; Contractile force; Female; Heart auricle; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Male; Middle Aged; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria, Heart - drug effects; Mitochondria, Heart - metabolism; Muscle Contraction - drug effects; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Myocardial Contraction - drug effects; Myocardium - metabolism; Skeletal muscle; Heart auricle; Cardiac muscle; Contractile force; Skeletal muscle; Cellular respiration
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2024.117492

The success of statin therapy in reducing cardiovascular morbidity and mortality is contrasted by the skeletal muscle complaints, which often leads to nonadherence. Previous studies have shown that inhibition of mitochondrial function plays a key role in statin intolerance. Recently, it was found that statins may also influence energy metabolism in cardiomyocytes. This study assessed the effects of statin use on cardiac muscle ex vivo from patients using atorvastatin, rosuvastatin, simvastatin or pravastatin and controls. Cardiac tissue and skeletal muscle tissue were harvested during open heart surgery after patients provided written informed consent. Patients included were undergoing cardiac surgery and either taking statins (atorvastatin, rosuvastatin, simvastatin or pravastatin) or without statin therapy (controls). Contractile behaviour of cardiac auricles was tested in an ex vivo set-up and cellular respiration of both cardiac and skeletal muscle tissue samples was measured using an Oxygraph-2k. Finally, statin acid and lactone concentrations were quantified in cardiac and skeletal homogenates by LC-MS/MS. Fatty acid oxidation and mitochondrial complex I and II activity were reduced in cardiac muscle, while contractile function remained unaffected. Inhibition of mitochondrial complex III by statins, as previously described, was confirmed in skeletal muscle when compared to control samples, but not observed in cardiac tissue. Statin concentrations determined in skeletal muscle tissue and cardiac muscle tissue were comparable. Statins reduce skeletal and cardiac muscle cell respiration without significantly affecting cardiac contractility. •Statins reduce mitochondrial CIII respiration in skeletal muscle under CI and CII inhibition.•Statins reduce FAO and mitochondrial CI and II respiration in cardiac muscle.•Statins do not significantly influence ex vivo contractile function of cardiac muscle.•Statin acid and lactone concentrations were comparable in cardiac and skeletal muscle.