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Nifedipine improves the migratory ability of circulating endothelial progenitor cells depending on manganese superoxide dismutase upregulation.

Abstract

BACKGROUND
Migratory ability of resident endothelial cells and their circulating progenitors, that is endothelial progenitor cells (EPCs), represent a crucial event in vascular repairing processes. Although oxidants are known to counteract the migratory ability of resident endothelial cells, their possible role in modulating EPC motility is unknown. EPCs exhibit stronger resistance to oxidants than mature endothelial cells mainly because of higher expression of manganese (Mn) superoxide dismutase (SOD). As nifedipine is a dihydropyridine calcium antagonist known to enhance MnSOD expression in mature endothelial cells, we investigated the effects of nifedipine on MnSOD expression and motility in EPCs.
METHODS AND RESULTS
EPCs were isolated from peripheral blood of healthy donors and cultured in fibronectin-coated flasks. Nifedipine improved both motility of cultured EPCs (+55% vs. control, P = 0.007) and their adhesion to tumor necrosis factor-alpha-activated mature endothelial cells (+33% vs. control, P = 0.03). Reduction of EPC dichlorofluorescein content (-32% vs. control, P = 0.009) and a parallel increase in nitrite plus nitrate concentration in EPC supernatants (+25% vs. control, P = 0.009) were also observed. The study of SOD showed a nifedipine-dependent upregulation of MnSOD in a time-dependent and dose-dependent manner. MnSOD expression blockade by RNA interference abolished nifedipine effect on EPC motility. Although nifedipine also increased vascular endothelial growth factor (VEGF) release from EPCs, its effect on EPC motility was unaffected by an anti-VEGF antibody.
CONCLUSION
Nifedipine improves EPC motility due to MnSOD upregulation. The capability of this dihydropyridine calcium antagonist to reduce cardiovascular events might also be related to improved EPC function.

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  • Publisher Full Text

    • Authors

    Passacquale G, Desideri G, Croce G, Murgo S, Mancarelli MM, Zazzeroni F, Alesse E, Ferri C

    Institution

    Department of Internal Medicine and Public Health, University of L'Aquila, L'Aquila, Italy.

    Source

    Journal of hypertension 26:4 2008 Apr pg 737-46

    MeSH

    Adult
    Calcium Channel Blockers
    Cell Adhesion
    Cell Movement
    Cells, Cultured
    Endothelial Cells
    Gene Expression Regulation, Enzymologic
    Humans
    Nifedipine
    Nitrates
    Nitrites
    Oxidative Stress
    Stem Cells
    Superoxide Dismutase
    Up-Regulation
    Vascular Endothelial Growth Factor A

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    18327084