Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Circ Res. 2012 Jun 22;111(1):87-96. doi: 10.1161/CIRCRESAHA.112.270215. Epub 2012 May 1.
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 (H(2)O(2)) 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.
We aimed to examine whether BM plays a role in modulating microvascular endothelial and metabolic functions in mice, and if so, to elucidate the mechanisms involved.
Male eNOS(-/-) mice were transplanted with BM cells from wild-type (WT) or eNOS(-/-) mice and were maintained for 6 weeks. Endothelium-dependent relaxations and hyperpolarizations of mesenteric arteries to acetylcholine were reduced in eNOS(-/-) mice and were markedly improved when transplanted with WT-BM but not with eNOS(-/-)-BM. The enhanced component of endothelium-dependent relaxations was abolished by catalase, indicating that the improved responses were mediated by H(2)O(2). In contrast, no such beneficial effect was noted in the aorta. Reduced plasma adiponectin levels and impaired glucose tolerance in eNOS(-/-) mice were also improved by WT-BM transplantation. Neuronal nitric oxide synthase (nNOS) in mesenteric arteries of eNOS(-/-) mice was significantly upregulated only when transplanted with WT-BM. Importantly, the beneficial effects of WT-BM transplantation were absent in eNOS(-/-)/adiponectin(-/-) or eNOS(-/-)/nNOS(-/-) mice.
These results provide the first evidence that BM plays an important role in modulating microvascular endothelial and metabolic functions, for which adiponectin and nNOS may be involved.
我们之前已经证明，随着血管管径的减小，内皮衍生超极化因子（EDHF）的重要性增加，并且内皮衍生的过氧化氢（H₂O₂）是动物和人体内的 EDHF，其主要来源是内皮型一氧化氮合酶（eNOS）。最近的研究表明，骨髓（BM）在调节心血管和代谢功能方面起着重要作用。
我们旨在研究 BM 是否在调节小鼠的微血管内皮和代谢功能方面发挥作用，如果是，阐明其涉及的机制。
雄性 eNOS（-/-）小鼠接受来自野生型（WT）或 eNOS（-/-）小鼠的 BM 细胞移植，并维持 6 周。eNOS（-/-）小鼠的肠系膜动脉对乙酰胆碱的内皮依赖性松弛和超极化作用减弱，当移植 WT-BM 时明显改善，但移植 eNOS（-/-）-BM 时则不然。过氧化氢酶消除了增强的内皮依赖性松弛成分，表明改善的反应是由 H₂O₂介导的。相比之下，在主动脉中没有观察到这种有益的作用。eNOS（-/-）小鼠的血浆脂联素水平降低和葡萄糖耐量受损也通过 WT-BM 移植得到改善。eNOS（-/-）小鼠的肠系膜动脉中的神经元型一氧化氮合酶（nNOS）仅在移植 WT-BM 时显著上调。重要的是，在 eNOS（-/-）/脂联素（-/-）或 eNOS（-/-）/nNOS（-/-）小鼠中，WT-BM 移植的有益作用不存在。
这些结果首次提供了证据，表明 BM 在调节微血管内皮和代谢功能方面起着重要作用，脂联素和 nNOS 可能参与其中。
