Increased myoendothelial feedback is associated with increased connexin37 and IK1 channel expression in mesenteric arteries of diet-induced hyperhomocysteinemic mice.
Increased myoendothelial feedback is associated with increased connexin37 and IK1 channel expression in mesenteric arteries of diet-induced hyperhomocysteinemic mice.
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肌内皮反馈的增加与饮食诱导的高同型半胱氨酸血症小鼠肠系膜动脉中连接蛋白 37 和 IK1 通道表达的增加有关。
DOI：
10.1111/micc.12398
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Guraya,Monique
中科院分区：
文献类型：
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作者：
Looft-Wilson,RobinC;Goodell,CaraR;Mutch,ChristinaA;Mutchler,StephanieM;Miller,KaylaL;Guraya,Monique
先前，我们发现饮食诱导的小鼠HHcy导致肠系膜动脉中eNOS表达和信号转导减少，但大大增强了非NOS，非前列环素依赖性血管舒张，这涉及MEJ通讯。为了进一步评估是否高同型半胱氨酸增强MEJ通信，本研究探讨内皮依赖性衰减苯肾上腺素诱导的血管收缩（肌内皮反馈）和关键molecules involved.MethodsMyoendothelial反馈进行了检查，在离体小鼠肠系膜动脉，6周饮食诱导的高同型半胱氨酸，使用压力myography。采用免疫印迹法测定间隙连接（Cx37、Cx40、Cx43）、NOS（eNOS、nNOS、iNOS）和钾通道（IK1）蛋白表达，采用真实的时间PCR法测定连接蛋白mRNA。使用药物TRIM.ResultsMyoendothelial反馈显着（P< .05）增强HHcy动脉相比，对照组，符合显着更大的Cx37和IK1蛋白和Cx37 mRNA的nNOS + iNOS血管反应的贡献进行了评估。Cx43蛋白，而不是mRNA，在HHcy中显着减少，Cx40没有什么不同。eNOS蛋白在HHcy组明显减少。nNOS和iNOS无差异。TRIM对血管功能的影响不大。结论饮食诱导的HHcy增强了肌内皮反馈，Cx37和IK1表达增加可能起作用。nNOS或iNOS不上调以补偿eNOS的减少，并且它们几乎不参与血管功能。
ObjectivePreviously, we found that diet‐induced HHcy in mice caused decreased eNOS expression and signaling in mesenteric arteries, but greatly enhanced non‐NOS, non‐prostacyclin‐dependent vasodilation, which involves MEJ communication. To further assess whether HHcy enhances MEJ communication, this study examined endothelium‐dependent attenuation of phenylephrine‐induced vasoconstriction (myoendothelial feedback) and key molecules involved.MethodsMyoendothelial feedback was examined in isolated mouse mesenteric arteries, after 6‐weeks diet‐induced HHcy, using pressure myography. Gap junction (Cx37, Cx40, Cx43), NOS (eNOS, nNOS, iNOS), and potassium channel (IK1) protein expression were measured with immunoblots, and connexin mRNAs with real‐time PCR. Contribution of nNOS + iNOS to vasomotor responses was assessed using the drug TRIM.ResultsMyoendothelial feedback was significantly (P< .05) enhanced in HHcy arteries compared to control, coincident with significantly greater Cx37 and IK1 protein and Cx37 mRNA. Cx43 protein, but not mRNA, was significantly less in HHcy, and Cx40 was not different. eNOS protein was significantly less in HHcy. nNOS and iNOS were not different. TRIM had little effect on vasomotor function.ConclusionsDiet‐induced HHcy enhanced myoendothelial feedback, and increased Cx37 and IK1 expression may contribute. nNOS or iNOS did not upregulate to compensate for decreased eNOS, and they had little involvement in vasomotor function.