Wang Han, Tao Ling, Ambrosio Anastasia, Yan Wenjun, Summer Ross, Lau Wayne Bond, Wang Yajing, Ma Xinliang
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 147 West Changle Rd, Xi'an, 710032, Shaanxi, China.
Department of Emergency Medicine, Thomas Jefferson University, 1025 Walnut Street, 808 College Building, Philadelphia, PA, 19107, USA.
Cardiovasc Diabetol. 2017 Jan 19;16(1):12. doi: 10.1186/s12933-016-0488-0.
Endothelial dysfunction plays a critical role in the development of type 2 diabetes (T2DM). T-cadherin (T-cad) has gained recognition as a regulator of endothelial cell (EC) function. The present study examined whether T-cad deficiency increases vascular vulnerability in T2DM.
Vascular segments were isolated from WT or T-cad knockout mice. Endothelial function, total NO accumulation, and the expression of T-cad related proteins were determined.
Ach and acidified NaNO2 induced similar vasorelaxation in WT groups. T-cad KO mice exhibited normal response to acidified NaNO2, but manifested markedly reduced response to Ach. NO accumulation was also decreased in T-cad KO group. T-cad expression was reduced in WT mice fed 8 weeks of high fat diet (HFD). Furthermore, exacerbated reduction of vasorelaxation was observed in T-cad KO mice fed 8 weeks of HFD.
In the current study, we provide the first in vivo evidence that T-cadherin deficiency causes endothelial dysfunction in T2DM vascular segments, suggesting the involvement of T-cad deficiency in T2DM pathogenesis.
内皮功能障碍在2型糖尿病（T2DM）的发生发展中起关键作用。T-钙黏蛋白（T-cad）已被公认为内皮细胞（EC）功能的调节因子。本研究探讨T-cad缺乏是否会增加T2DM中的血管易损性。
从小鼠野生型（WT）或T-cad基因敲除小鼠中分离血管段。测定内皮功能、总一氧化氮（NO）蓄积量以及T-cad相关蛋白的表达。
乙酰胆碱（Ach）和酸化亚硝酸钠（NaNO2）在WT组中诱导相似的血管舒张。T-cad基因敲除小鼠对酸化NaNO2表现出正常反应，但对Ach的反应明显降低。T-cad基因敲除组的NO蓄积量也减少。喂食8周高脂饮食（HFD）的WT小鼠中T-cad表达降低。此外，喂食8周HFD的T-cad基因敲除小鼠中观察到血管舒张的进一步降低。
在本研究中，我们提供了首个体内证据，即T-钙黏蛋白缺乏导致T2DM血管段中的内皮功能障碍，提示T-cad缺乏参与T2DM发病机制。
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