Lee Michelle Hui-Hsin, Chen Shiu-Jen, Tsao Cheng-Ming, Wu Chin-Chen
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Department of Physiology, National Defense Medical Center, Taipei, Taiwan; Department of Nursing, Kang-Ning Junior College of Medical Care and Management, Taipei, Taiwan.
PLoS One. 2014 Jun 13;9(6):e99947. doi: 10.1371/journal.pone.0099947. eCollection 2014.
Perivascular adipose tissue (PVAT)-derived factors have been proposed to play an important role in the pathogenesis of atherosclerosis. Caveolin-1 (Cav-1), occupying the calcium/calmodulin binding site of endothelial NO synthase (eNOS) and then inhibiting nitric oxide (NO) production, is also involved in the development of atherosclerosis. Thus, we investigated whether PVAT regulated vascular tone via Cav-1 and/or endothelial NO pathways. Isometric tension studies were carried out in isolated thoracic aortas from Wistar rats in the presence and absence of PVAT. Concentration-response curves of phenylephrine, acetylcholine, and sodium nitroprusside were illustrated to examine the vascular reactivity and endothelial function. The protein expressions of eNOS and Cav-1 were also examined in aortic homogenates. Our results demonstrated that PVAT significantly enhanced vasoconstriction and inhibited vasodilatation via endothelium-dependent mechanism. The aortic NO production was diminished after PVAT treatment, whereas protein expression and activity of eNOS were not significantly affected. In addition, Cav-1 protein expression was significantly increased in aortas with PVAT transfer. Furthermore, a caveolae depleter methyl-β-cyclodextrin abolished the effect of PVAT on the enhancement of vasoconstriction, and reversed the impairment of aortic NO production. In conclusion, unknown factor(s) released from PVAT may inhibit endothelial NO production and induce vasocontraction via an increase of Cav-1 protein expression.
血管周围脂肪组织（PVAT）衍生因子被认为在动脉粥样硬化的发病机制中起重要作用。小窝蛋白-1（Cav-1）占据内皮型一氧化氮合酶（eNOS）的钙/钙调蛋白结合位点，进而抑制一氧化氮（NO）生成，它也参与动脉粥样硬化的发展。因此，我们研究了PVAT是否通过Cav-1和/或内皮型NO途径调节血管张力。在有或无PVAT存在的情况下，对来自Wistar大鼠的离体胸主动脉进行等长张力研究。绘制去氧肾上腺素、乙酰胆碱和硝普钠的浓度-反应曲线，以检测血管反应性和内皮功能。还检测了主动脉匀浆中eNOS和Cav-1的蛋白表达。我们的结果表明，PVAT通过内皮依赖性机制显著增强血管收缩并抑制血管舒张。PVAT处理后主动脉NO生成减少，而eNOS的蛋白表达和活性未受到显著影响。此外，在转移了PVAT的主动脉中，Cav-1蛋白表达显著增加。此外，一种小窝耗竭剂甲基-β-环糊精消除了PVAT对血管收缩增强的作用，并逆转了主动脉NO生成的损害。总之，PVAT释放的未知因子可能通过增加Cav-1蛋白表达来抑制内皮型NO生成并诱导血管收缩。
