Nitric oxide-donating statin improves multiple functions of circulating angiogenic cells

G. Mangialardi, A. Monopoli, E. Ongini, G. Spinetti, O. Fortunato, C. Emanueli, P. Madeddu

Research output: Contribution to journalArticle

Abstract

BACKGROUND AND PURPOSE Statins, a major component of the prevention of cardiovascular disease, aid progenitor cell functions in vivo and in vitro. Statins bearing a NO-releasing moiety were developed for their enhanced anti-inflammatory/anti-thrombotic properties. Here, we investigated if the NO-donating atorvastatin (NCX 547) improved the functions of circulating angiogenic cells (CACs). EXPERIMENTAL APPROACH Circulating angiogenic cells (CACs) were prepared from peripheral blood monocytes of healthy volunteers and type-2 diabetic patients and were cultured in low (LG) or high glucose (HG) conditions, 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 the endothelial NOS inhibitor L-NIO, the NO scavenger c-PTIO or vehicle. KEY RESULTS 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-cultured CACs, while atorvastatin prevented only apoptosis in CACs. The activity of Akt, a pro-survival kinase, was increased by atorvastatin in LG-cultured but not in HG-cultured CACs, whereas NCX 547 increased Akt activity in both conditions. L-NIO partially blunted and c-PTIO prevented NCX 547-induced improvements in CAC functions. Finally, NCX 547 improved outgrowth and migration of CACs prepared from patients with type 2 diabetes. CONCLUSIONS AND IMPLICATIONS 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-releasing statins more effective agents for treating cardiovascular disease.

Original languageEnglish
Pages (from-to)570-583
Number of pages14
JournalBritish Journal of Pharmacology
Volume164
Issue number2 B
DOIs
Publication statusPublished - Sep 2011

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Nitric Oxide
Glucose
Apoptosis
Cardiovascular Diseases
Cell Aging
6-(nitrooxy)hexyl 7-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl)-3,5-dihydroxyheptanoate
Type 2 Diabetes Mellitus
Monocytes
Healthy Volunteers
Anti-Inflammatory Agents
Phosphotransferases
Stem Cells
Atorvastatin Calcium

Keywords

  • angiogenesis
  • circulating angiogenic cells
  • diabetes
  • NO
  • statin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Nitric oxide-donating statin improves multiple functions of circulating angiogenic cells. / Mangialardi, G.; Monopoli, A.; Ongini, E.; Spinetti, G.; Fortunato, O.; Emanueli, C.; Madeddu, P.

In: British Journal of Pharmacology, Vol. 164, No. 2 B, 09.2011, p. 570-583.

Research output: Contribution to journalArticle

Mangialardi, G. ; Monopoli, A. ; Ongini, E. ; Spinetti, G. ; Fortunato, O. ; Emanueli, C. ; Madeddu, P. / Nitric oxide-donating statin improves multiple functions of circulating angiogenic cells. In: British Journal of Pharmacology. 2011 ; Vol. 164, No. 2 B. pp. 570-583.
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AU - Mangialardi, G.

AU - Monopoli, A.

AU - Ongini, E.

AU - Spinetti, G.

AU - Fortunato, O.

AU - Emanueli, C.

AU - Madeddu, P.

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