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Statins bearing a NO\u2010releasing moiety were developed for their enhanced anti\u2010inflammatory\/anti\u2010thrombotic properties. Here, we investigated if the NO\u2010donating atorvastatin (NCX 547) improved the functions of circulating angiogenic cells (CACs).<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold>Circulating angiogenic cells (CACs) were prepared from peripheral blood monocytes of healthy volunteers and type\u20102 diabetic patients and were cultured in low (LG) or high glucose (HG) conditions, in presence of atorvastatin or NCX 547 (both at 0.1\u2003\u00b5M) or vehicle. Functional assays (outgrowth, proliferation, viability, senescence and apoptosis) were performed in presence of the endothelial NOS inhibitor L\u2010NIO, the NO scavenger c\u2010PTIO or vehicle.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold>Culturing in HG conditions lowered NO in CACs, inhibited outgrowth, proliferation, viability and migration, and induced cell senescence and apoptosis. NCX 547 fully restored NO levels and functions of HG\u2010cultured CACs, while atorvastatin prevented only apoptosis in CACs. The activity of Akt, a pro\u2010survival kinase, was increased by atorvastatin in LG\u2010cultured but not in HG\u2010cultured CACs, whereas NCX 547 increased Akt activity in both conditions. L\u2010NIO partially blunted and c\u2010PTIO prevented NCX 547\u2010induced improvements in CAC functions. Finally, NCX 547 improved outgrowth and migration of CACs prepared from patients with type 2 diabetes.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold>NCX 547 was more effective than atorvastatin in preserving functions of CACs. This property adds to the spectrum of favourable actions that would make NO\u2010releasing statins more effective agents for treating cardiovascular disease.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01423.x","type":"journal-article","created":{"date-parts":[[2011,4,12]],"date-time":"2011-04-12T10:33:33Z","timestamp":1302604413000},"page":"570-583","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Nitric oxide\u2010donating statin improves multiple functions of circulating angiogenic 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