Abstract 15267: Evidence for the Important Role of the Bone Marrow in Modulating Microvascular Endothelial 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 the nature of EDHF in mouse microvessels is hydrogen peroxide (H2O2) 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 microvascular endothelial functions in mice.
Methods and Results: Wild-type (WT) and eNOS−/− mice of 8-weeks of age were injected with BM cells from WT or eNOS−/− mice after X-lay irradiation (n=8 each). After 6 weeks, we examined endothelium-dependent relaxations of isolated mesenteric arteries and the aorta in organ chamber experiments. We also measured plasma levels of adiponectin, cholesterol, triglyceride, and fasting blood glucose. 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, whereas the responses were unchanged in WT mice when transplanted with WT-BM. The enhanced component of endothelium-dependent relaxations was noted in the presence of indomethacin and L-NNA and was inhibited by catalase, indicating that the improved component was mediated by EDHF/H2O2. In contrast, no such beneficial effect of WT-BM transplantation was noted in the aorta of eNOS−/− mice. Plasma adiponectin level was significantly decreased in eNOS−/− mice compared with WT mice (15.7 vs. 20.1 μg/ml, P<0.05) and was significantly improved when transplanted with WT-BM (19.1 μg/ml, P<0.05 vs. untreated eNOS−/−). 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), whereas no change was noted for plasma levels of triglyceride or fasting blood glucose.
Conclusions: These results provide the evidence that BM plays an important role in modulating microvascular endothelial functions, especially EDHF/H2O2-mediated component, for which the increase in adiponectin levels may be involved.
- © 2010 by American Heart Association, Inc.