1. T-cadherin deficiency increases vascular vulnerability in T2DM through impaired NO bioactivity
- Author
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Xin-Liang Ma, Han Wang, Yajing Wang, Ling Tao, Wenjun Yan, Wayne Bond Lau, Anastasia Ambrosio, and Ross Summer
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Vasodilator Agents ,Endocrinology, Diabetes and Metabolism ,T2DM ,030204 cardiovascular system & hematology ,Diet, High-Fat ,Nitric Oxide ,Pathogenesis ,Mice ,03 medical and health sciences ,Organ Culture Techniques ,0302 clinical medicine ,Endothelial cell ,Internal medicine ,medicine ,Animals ,Endothelial dysfunction ,cardiovascular diseases ,Vascular ring ,Aorta ,Original Investigation ,Mice, Knockout ,business.industry ,Cadherins ,T-cadherin ,NO bioactivity ,medicine.disease ,Vasodilation ,Vascular endothelial growth factor B ,Endothelial stem cell ,Vascular endothelial growth factor A ,030104 developmental biology ,Endocrinology ,Diabetes Mellitus, Type 2 ,Vascular endothelial growth factor C ,Knockout mouse ,Endothelium, Vascular ,business ,Cardiology and Cardiovascular Medicine - Abstract
Background 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. Methods 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. Results 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. Conclusions 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.
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