YAP-galectin-3 signaling mediates endothelial dysfunction in angiotensin II-induced hypertension in mice.

Autor: Pang ZD; Department of Physiology and Pathophysiology, Cardiovascular Research Centre, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China.; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China., Sun X; Department of Physiology and Pathophysiology, Cardiovascular Research Centre, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China.; School of Basic and Medical Sciences, Xi'an Medical University, 1 Xinwang Road, Xi'an, 710021, Shaanxi, China., Bai RY; Department of Physiology and Pathophysiology, Cardiovascular Research Centre, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China., Han MZ; Department of Physiology and Pathophysiology, Cardiovascular Research Centre, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China., Zhang YJ; Department of Physiology and Pathophysiology, Cardiovascular Research Centre, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China.; Department of Cardiac Surgery, The First Affiliated Hospital, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China., Wu W; Department of Physiology and Pathophysiology, Cardiovascular Research Centre, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China., Zhang Y; Department of Physiology and Pathophysiology, Cardiovascular Research Centre, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China., Lai BC; Department of Physiology and Pathophysiology, Cardiovascular Research Centre, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China., Zhang Y; Department of Physiology and Pathophysiology, Cardiovascular Research Centre, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China., Wang Y; Department of Physiology and Pathophysiology, Cardiovascular Research Centre, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China., Du XJ; Department of Physiology and Pathophysiology, Cardiovascular Research Centre, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China. xiao-jun.du@baker.edu.au., Deng XL; Department of Physiology and Pathophysiology, Cardiovascular Research Centre, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China. dengxl@mail.xjtu.edu.cn.; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University Health Science Center, 76 West Yanta Road, Xi'an, 710061, Shaanxi, China. dengxl@mail.xjtu.edu.cn.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2023 Jan 11; Vol. 80 (2), pp. 38. Date of Electronic Publication: 2023 Jan 11.
DOI: 10.1007/s00018-022-04623-5
Abstrakt: Background: Vascular endothelial dysfunction is regarded as an early event of hypertension. Galectin-3 (Gal-3) is known to participate in various pathological processes. Whilst previous studies showed that inhibition of Gal-3 effectively ameliorates angiotensin II (Ang II)-induced atherosclerosis or hypertension, it remains unclear whether Ang II regulates Gal-3 expression and actions in vascular endothelium.
Methods: Using techniques of molecular biology and myograph, we investigated Ang II-mediated changes in Gal-3 expression and activity in thoracic aortas and mesenteric arteries from wild-type and Gal-3 gene deleted (Gal-3 -/- ) mice and cultured endothelial cells.
Results: The serum level of Gal-3 was significantly higher in hypertensive patients or in mice with chronic Ang II-infusion. Ang II infusion to wild-type mice enhanced Gal-3 expression in the aortic and mesenteric arteries, elevated systolic blood pressure and impaired endothelium-dependent relaxation of the thoracic aortas and mesenteric arteries, changes that were abolished in Gal-3 -/- mice. In human umbilical vein endothelial cells, Ang II significantly upregulated Gal-3 expression by promoting nuclear localization of Yes-associated protein (YAP) and its interaction with transcription factor Tead1 with enhanced YAP/Tead1 binding to Gal-3 gene promoter region. Furthermore, Gal-3 deletion augmented the bioavailability of nitric oxide, suppressed oxidative stress, and alleviated inflammation in the thoracic aorta of Ang II-infused mice or endothelial cells exposed to Ang II.
Conclusions: Our results demonstrate for the first time that Ang II upregulates Gal-3 expression via increment in YAP nuclear localization in vascular endothelium, and that Gal-3 mediates endothelial dysfunction contributing to the development of hypertension.
(© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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