Statins affect human iPSC-derived cardiomyocytes by interfering with mitochondrial function and intracellular...

Area of Science:

• Cardiology
• Molecular Biology
• Pharmacology

Background:

• Statins effectively reduce cardiovascular events by inhibiting cholesterol synthesis.
• Statin-induced muscle complaints are linked to mitochondrial dysfunction.
• An aging population with compromised cardiac function necessitates understanding statin effects on cardiomyocytes.

Purpose of the Study:

• To investigate the impact of common statins on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-derived CMs).
• To evaluate cellular viability, metabolic capacity, and mitochondrial function following statin exposure.

Main Methods:

• hiPSC-derived CMs were treated with simvastatin, atorvastatin, rosuvastatin, and cerivastatin at varying concentrations.
• Cellular viability, respiration, membrane potential, and morphology were assessed using metabolic assays and fluorescent microscopy.

Main Results:

• Simvastatin and atorvastatin significantly reduced cardiomyocyte viability (42-64%) and inhibited basal and maximal respiration.
• Simvastatin lactone demonstrated the most potent inhibition of respiration.
• Mitochondrial membrane potential was decreased by simvastatin and atorvastatin.

Conclusions:

• Certain statins, particularly simvastatin, negatively affect cardiomyocyte viability and mitochondrial function.
• Hydrophilic statins like atorvastatin acid showed less impact on cardiomyocyte metabolism.
• Further research is needed to guide clinical statin prescribing, especially for vulnerable patient groups.