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C1q/tumor necrosis factor-related protein-3 improves microvascular endothelial function in diabetes through the AMPK/eNOS/NO· signaling pathway.
Yan, Zheyi; Cao, Xiaoming; Wang, Chunfang; Liu, Sha; Li, Yanjie; Lu, Gan; Yan, Wenjun; Guo, Rui; Zhao, Dajun; Cao, Jimin; Xu, Yong.
Afiliación
  • Yan Z; Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China; Department of Ophthalmology, First Hospital of Shanxi Medical University, Taiyuan, China; Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA, United States; Key Laboratory of Cellular
  • Cao X; Department of Orthopedics, Shanxi Medical University Second Affiliated Hospital, Taiyuan, China.
  • Wang C; Department of Ophthalmology, First Hospital of Shanxi Medical University, Taiyuan, China.
  • Liu S; Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China.
  • Li Y; Department of Ophthalmology, First Hospital of Shanxi Medical University, Taiyuan, China.
  • Lu G; Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA, United States; Laboratory of Emergency Medicine, Department of Emergency Medicine, Sichuan University West China Hospital, Chengdu, China.
  • Yan W; Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA, United States; Department of Cardiology, Xijing Hospital, Xian, China.
  • Guo R; Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA, United States; Morphology Laboratory, Shanxi Medical University, Taiyuan, China.
  • Zhao D; Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA, United States; Department of Cardiac Surgery, Zhongshan Hospital Fudan University, Shanghai, China.
  • Cao J; Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, China.
  • Xu Y; Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China. Electronic address: xuyong@sxmu.edu.cn.
Biochem Pharmacol ; 195: 114745, 2022 01.
Article en En | MEDLINE | ID: mdl-34454930
The repair of vascular endothelial cell dysfunction is an encouraging approach for the treatment of vascular complications associated with diabetes. It has been demonstrated that members of C1q/tumor necrosis factor-related protein (CTRP) family may improve endothelial function. Nevertheless, the protective properties of CTRPs in diabetic microvascular complications continue to be mostly unknown. Here, we demonstrate that the C1q-like globular domain of CTRP3, CTRP5, and CTRP9 (gCTRP3, 5, 9) exerted a vasorelaxant effect on the microvasculature, of which gCTRP3 was the most powerful one. In a murine model of type 2 diabetes mellitus, serum gCTRP3 level and endothelial function decreased markedly compared with controls. Two weeks of gCTRP3 treatment (0.5 µg/g/d) enhanced endothelium-dependent relaxation in microvessels, increased nitric oxide (NO·) production, and reduced retinal vascular leakage. In addition, Western blotting in human retinal microvascular endothelial cells indicated that gCTRP3 triggered AMP-activated protein kinase-α (AMPKα), hence increasing the endothelial NO synthase (eNOS) level and NO· production. In addition, incubation with gCTRP3 in vitro ameliorated the endothelial dysfunction induced by high glucose in the branch of the mesenteric artery. Blockade of either eNOS or AMPKα completely abolished the effects of gCTRP3 described above. Taken together, we demonstrate for the first time that gCTRP3 improves impaired vasodilatation of microvasculature in diabetes by ameliorating endothelial cell function through the AMPK/eNOS/NO· signaling pathway. This finding may suggest an effective intervention against diabetes-associated microvascular complications.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Células Endoteliales / Diabetes Mellitus Tipo 2 / Óxido Nítrico Sintasa de Tipo III / Adipoquinas / Proteínas Quinasas Activadas por AMP / Óxido Nítrico Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Biochem Pharmacol Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Células Endoteliales / Diabetes Mellitus Tipo 2 / Óxido Nítrico Sintasa de Tipo III / Adipoquinas / Proteínas Quinasas Activadas por AMP / Óxido Nítrico Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Biochem Pharmacol Año: 2022 Tipo del documento: Article Pais de publicación: Reino Unido