title: T-cadherin deficiency increases vascular vulnerability in T2DM through impaired NO bioactivity.
abstract: 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.
authors.affiliation: 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.
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 147 West Changle Rd, Xi'an, 710032, Shaanxi, China. lingtaoxjcardio@163.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Tao
authors.affiliation: Department of Emergency Medicine, Thomas Jefferson University, 1025 Walnut Street, 808 College Building, Philadelphia, PA, 19107, USA.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Ambrosio
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 147 West Changle Rd, Xi'an, 710032, Shaanxi, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Medicine, Thomas Jefferson University, 1025 Walnut Street, College Building, Philadelphia, PA, 19107, USA.
authors.forename: Ross
authors.initials: R
authors.lastname: Summer
authors.affiliation: Department of Emergency Medicine, Thomas Jefferson University, 1025 Walnut Street, 808 College Building, Philadelphia, PA, 19107, USA.
authors.forename: Wayne Bond
authors.initials: WB
authors.lastname: Lau
authors.affiliation: Department of Emergency Medicine, Thomas Jefferson University, 1025 Walnut Street, 808 College Building, Philadelphia, PA, 19107, USA.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, Thomas Jefferson University, 1025 Walnut Street, 808 College Building, Philadelphia, PA, 19107, USA. xin.ma@jefferson.edu.
authors.forename: Xinliang
authors.initials: X
authors.lastname: Ma
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D015820:Cadherins / Q000172:deficiency*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D059305:Diet, High-Fat / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D009924:Organ Culture Techniques; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D015820:Cadherins; C099972:H-cadherin; D014665:Vasodilator Agents; D009569:Nitric Oxide
keywords: Endothelial cell; Endothelial dysfunction; NO bioactivity; T-cadherin; T2DM; Vascular ring