• Cardiovascular research · Mar 2012

    Endothelial nitric oxide synthase of the bone marrow regulates myocardial hypertrophy, fibrosis, and angiogenesis.

    • Andrey Kazakov, Patrick Müller, Philippe Jagoda, Alexander Semenov, Michael Böhm, and Ulrich Laufs.
    • Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, 66424 Homburg/Saar, Germany. andrej.kasakow@uniklinikum-saarland.de
    • Cardiovasc. Res. 2012 Mar 1; 93 (3): 397-405.

    AimsThe endothelial nitric oxide synthase (eNOS) regulates the mobilization and function of endothelial progenitor cells (EPC). We hypothesized that eNOS of the bone marrow (BM) affects cardiac remodelling during myocardial hypertrophy via the regulation of BM-derived vascular progenitor cells.Methods And ResultsTen-week-old male C57/Bl6 wild-type (WT) and eNOS mice (eNOS(-/-)) were subjected to transverse aortic constriction (TAC, 360 μm, 35 days) or sham operation inducing cardiac hypertrophy and increasing the numbers of Ki67+ cardiomyocytes in both strains. Myocardial fibrosis was more pronounced in eNOS(-/-) TAC (3.4 ± 0.4 vs. 2.1 ± 0.2% in WT-TAC, P < 0.05). TAC up-regulated the number of EPCs in the peripheral blood and in the BM in WT but not in eNOS(-/-). Baseline migratory capacity of EPCs was lower in eNOS(-/-) and was not raised by TAC in either strain. To test the role of eNOS in the BM during pressure overload, strain-mismatched (WT/eNOS(-/-); eNOS(-/-)/WT) and strain-matched (WT/WT; eNOS(-/-)/eNOS(-/-)) BM transplantations (BMTs) were performed. Cardiac hypertrophy was most pronounced in WT/eNOS(-/-) TAC. Strain-mismatched BMT of eNOS(-/-) BM deteriorated and of WT BM ameliorated cardiac fibrosis, capillary density, the numbers of EPCs in the peripheral blood and in the BM, and their migratory capacity in pressure overload. Following transplantation of green fluorescent protein (GFP)-positive BM, TAC increased the number of BM-derived podocalyxin(pos)GFP(pos) endothelial cells in both strains.ConclusioneNOS of the BM plays a key role for amelioration of cardiac hypertrophy, capillary density, and fibrosis during increased afterload.

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