Increasing muscle mass improves vascular function in obese (db/db) mice.
Increasing muscle mass improves vascular function in obese (db/db) mice.
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DOI：
10.1161/jaha.114.000854
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发表时间：
2014-06-25
影响因子：
5.4
通讯作者：
Stepp DW
中科院分区：
文献类型：
--
作者：
Qiu S;Mintz JD;Salet CD;Han W;Giannis A;Chen F;Yu Y;Su Y;Fulton DJ;Stepp DW
久坐的生活方式是心血管疾病的独立危险因素，运动已被证明可以缓解这种风险。缺乏运动与肌肉质量的丧失有关，而等长运动训练也可以逆转这一点。肌肉质量和血管功能之间的关系还不清楚。本研究的目的是确定通过肌肉生长的负调控因子--肌肉生长抑制素基因缺失而增加的肌肉质量是否会影响肥胖db/db小鼠肠系膜动脉的血管功能。肥胖小鼠骨骼肌中的肌肉生长抑素表达增加，并与肌肉质量减少(30%至50%)相关。肌肉抑制素缺失通过增加肌肉纤维大小增加了瘦(40%到60%)和肥胖(80%到115%)小鼠的肌肉质量(P<；0.05)。肌肉生长抑制素缺失减少了瘦小鼠的脂肪组织，但不是肥胖小鼠。在肥胖的肌肉生长抑素基因敲除小鼠中，胰岛素抵抗和葡萄糖耐量的标记物得到了改善。与瘦小鼠相比，肥胖小鼠表现出内皮血管扩张受损。这种损伤可以通过模拟超氧化物歧化酶的坦波尔来改善。肌肉抑制素的缺失改善了肥胖小鼠肠系膜动脉内皮血管的扩张，但在瘦小鼠中却没有。这种改善被一氧化氮合酶抑制剂L-NG-硝基精氨酸甲酯(L-NAME)钝化。前列环素(PGI2)和内皮衍生超极化因子(EDHF)介导的血管扩张在肥胖小鼠中得到保留，不受肌肉生长抑素缺失的影响。在肥胖小鼠肠系膜内皮细胞中，肌抑素(RO)的表达增加，而在肥胖小鼠中，肌肉生长抑素基因的缺失下调了其表达。NADPH氧化酶抑制剂(GKT136901)可改善肥胖小鼠受损的血管扩张功能。增加四氢生物蝶呤水平的sepiapterin治疗改善了肥胖小鼠的血管扩张，这一改善被L的名字阻止。通过基因缺失myostatin来增加肌肉质量可以改善肥胖小鼠的NO-，但不是PGI2或EDHF介导的血管扩张；这种血管扩张的改善是通过下调超氧化物来实现的。
A sedentary lifestyle is an independent risk factor for cardiovascular disease and exercise has been shown to ameliorate this risk. Inactivity is associated with a loss of muscle mass, which is also reversed with isometric exercise training. The relationship between muscle mass and vascular function is poorly defined. The aims of the current study were to determine whether increasing muscle mass by genetic deletion of myostatin, a negative regulator of muscle growth, can influence vascular function in mesenteric arteries from obese db/db mice. Myostatin expression was elevated in skeletal muscle of obese mice and associated with reduced muscle mass (30% to 50%). Myostatin deletion increased muscle mass in lean (40% to 60%) and obese (80% to 115%) mice through increased muscle fiber size (P<0.05). Myostatin deletion decreased adipose tissue in lean mice, but not obese mice. Markers of insulin resistance and glucose tolerance were improved in obese myostatin knockout mice. Obese mice demonstrated an impaired endothelial vasodilation, compared to lean mice. This impairment was improved by superoxide dismutase mimic Tempol. Deletion of myostatin improved endothelial vasodilation in mesenteric arteries in obese, but not in lean, mice. This improvement was blunted by nitric oxide (NO) synthase inhibitor l‐NG‐nitroarginine methyl ester (l‐NAME). Prostacyclin (PGI2)‐ and endothelium‐derived hyperpolarizing factor (EDHF)‐mediated vasodilation were preserved in obese mice and unaffected by myostatin deletion. Reactive oxygen species) was elevated in the mesenteric endothelium of obese mice and down‐regulated by deletion of myostatin in obese mice. Impaired vasodilation in obese mice was improved by NADPH oxidase inhibitor (GKT136901). Treatment with sepiapterin, which increases levels of tetrahydrobiopterin, improved vasodilation in obese mice, an improvement blocked by l‐NAME. Increasing muscle mass by genetic deletion of myostatin improves NO‐, but not PGI2‐ or EDHF‐mediated vasodilation in obese mice; this vasodilation improvement is mediated by down‐regulation of superoxide.