Nitric oxide-donating statin improves multiple functions of circulating angiogenic cells
Background and purpose: Statins, a landmark in prevention of cardiovascular disease (CVD), aid progenitor cell functions in vivo and in vitro. Statins bearing a nitric oxide (NO) releasing moiety came into the focus for their enhanced anti-inflammatory/anti-thrombotic properties. Here, we investigated if the NO-donating atorvastatin NCX 547 improves the performance of circulating angiogenic cells (CACs).
Experimental approach: CACs from peripheral blood of healthy volunteers and type-2 diabetic patients were cultured in low (LG) or high glucose (HG), in presence of atorvastatin or NCX 547 (both at 0.1 µM) or vehicle. Functional assays (outgrowth, proliferation, viability, senescence and apoptosis) were performed in presence of endothelial NO synthase (eNOS) inhibitor LNIO, NO scavenger c-PTIO or vehicle.
Key results: HG reduced NO levels in CACs, inhibited outgrowth, proliferation, viability and migration, and induced cell senescence and apoptosis. NCX 547 fully restored NO levels and functionality of HG-cultured CACs, while atorvastatin prevented only CAC apoptosis. The activity of the pro-survival kinase and statin's target Akt was increased by atorvastatin in LG-cultured but not in HG-cultured CACs, whereas NCX 547 increased Akt activity in both conditions. LNIO partially blunted and c-PTIO abrogated NCX 547-induced improvement in CAC functions. Finally, NCX 547 improved outgrowth and migration of CACs in diabetic patients.
Conclusions and implications: Our study indicates the NCX 547 is superior to atorvastatin in preservation of CAC functions. This property adds to the spectrum of favourable actions that make NO-releasing statin an improved agent for CVD treatment.