Key result
Atorvastatin inhibits calcification in mesenchymal stromal cells but promotes it in smooth muscle-like cells.
Atorvastatin exerts cell type-specific effects on calcification in vitro, decreasing it in mesenchymal stromal cells while increasing it in smooth muscle cell-like cells, highlighting the importance of cellular heterogeneity in plaque stability.
Statins are widely prescribed to those with atherosclerosis to lower cholesterol and reduce cardiovascular risk, but their influence on plaque calcification remains unclear. While clinical data associate statin use with increased calcium scores and reduced cardiovascular events, their effect on rupture-prone microcalcifications has not been clinically assessed due to imaging limitations. In vitro studies report conflicting outcomes on statin-induced calcification in various cell types. To address this gap, we investigated the impact of atorvastatin on calcification across multiple plaque-relevant cell types using both monolayer cultures and a tissue-engineered 3D plaque model. Human mesenchymal stromal cells (MSCs) were isolated from iliac crest bone chips and differentiated into smooth muscle (mSMCs) cells using TGF-β1, while human vena saphena cells (HVSCs) were obtained from bypass surgery material. Monolayer cultures of MSCs, mSMCs, and HVSCs were exposed to calcifying medium with or without atorvastatin (0.1–1 μM) for 2 weeks. For the 3D model, cells were embedded in fibrin gels, cultured to form a collagenous matrix for 2 weeks, then calcified for an additional 2 weeks with or without atorvastatin (1–10 μM). In both monolayer and the 3D model, atorvastatin inhibited calcification in MSCs, while it induced calcification in mSMCs. For HVSCs, atorvastatin reduced calcification in 2D monolayer cultures, while it had no visible effect in 3D. This study highlights the cell type–specific effects of atorvastatin on calcification, underscoring the need to consider cellular heterogeneity when evaluating its impact on plaque stability. • The influence of atorvastatin on calcification potential was assessed in 2D and 3D • Atorvastatin decreased calcification in mesenchymal stromal cells • Atorvastatin increased calcification in smooth muscle cell-like cells • This underscores the need to consider cellular heterogeneity in atherosclerosis
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Jansen et al. (2026) studied Atherosclerosis. Atorvastatin vs. No atorvastatin was evaluated on Calcification. Atorvastatin inhibited calcification in mesenchymal stromal cells but induced calcification in smooth muscle cell-like cells across 2D and 3D models.
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