Abstract 10236: Evidence for the Important Role of the Bone Marrow in Modulating Microvascular Endothelial Responses and Metabolic Functions in Mice
Background: We have previously demonstrated that the importance of endothelium-derived hyperpolarizing factor (EDHF) increases as the vessel size decreases and that endothelium-derived hydrogen peroxide (H2O2) is an EDHF in animals and humans, for which endothelial nitric oxide synthase (eNOS) is the major source. Recent studies have suggested the important role of the bone marrow (BM) in modulating cardiovascular and metabolic functions. In this study, we thus examined the possible role of BM in modulating endothelial and metabolic functions in mice.
Methods and Results: Male eNOS-deficient (eNOS-/-) mice of 8-weeks of age were injected with BM cells from either wild-type (WT) or eNOS-/- mice after X-ray irradiation (n=8 each) and were maintained for 6 weeks. Endothelium-dependent relaxations of mesenteric arteries to acetylcholine were markedly reduced in eNOS-/- mice and were significantly improved when transplanted with WT-BM but not with eNOS-/--BM. The enhanced component of endothelium-dependent relaxations was resistant to indomethacin and L-NNA and was markedly inhibited by catalase, indicating that the improved EDHF component was mediated by H2O2. In contrast, no such beneficial effect of WT-BM transplantation was noted in the aorta of eNOS-/- mice. Plasma adiponectin level was significantly reduced in eNOS-/- mice compared with WT mice (15.3 vs. 21.2 μ g/ml, P<0.05) and was significantly improved when transplanted with WT-BM (18.7 μ g/ml, P<0.05 vs. untreated eNOS-/-) but not with eNOS-/--BM. Similarly, glucose tolerance was impaired in eNOS-/- mice and was ameliorated when transplanted with WT-BM (P<0.05). Plasma levels of total cholesterol and LDL-cholesterol in eNOS-/- mice were significantly reduced when transplanted with WT-BM (TC, 93.6 vs. 115.5 mg/dl, LDL-C, 7.6 vs. 12.8 mg/dl, both P<0.05). Neuronal nitric oxide synthase (nNOS) protein expression was significantly greater in mesenteric tissues of eNOS-/- mice transplanted with WT-BM compared with eNOS-/--BM, whereas it was comparable in the aorta.
Conclusion: These results provide the first evidence that BM plays an important role in modulating microvascular endothelial responses and metabolic functions, for which adiponectin and nNOS may be involved.
- Endothelium-derived relaxing factor
- Nitric oxide synthase
- Metabolic syndrome
- Reactive oxygen intermediates
- © 2011 by American Heart Association, Inc.