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

• Published in: Cellular and molecular life sciences : CMLS Vol. 80; no. 2; p. 38
• Main Authors: Pang, Zheng-Da, Sun, Xia, Bai, Ru-Yue, Han, Meng-Zhuan, Zhang, Yong-Jian, Wu, Wei, Zhang, Yu, Lai, Bao-Chang, Zhang, Yi, Wang, Yan, Du, Xiao-Jun, Deng, Xiu-Ling
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.02.2023; Springer Nature B.V
• Subjects: Angiotensin; Angiotensin II; Angiotensin II - metabolism; Angiotensin II - pharmacology; Animals; Aorta; Arteries; Arteriosclerosis; Atherosclerosis; Bioavailability; Biochemistry; Biomedical and Life Sciences; Biomedicine; Blood Pressure; Cell Biology; Endothelial cells; Endothelium; Endothelium, Vascular - metabolism; Galectin 3 - genetics; Galectin 3 - metabolism; Galectin-3; Gene deletion; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Hypertension; Hypertension - metabolism; Life Sciences; Localization; Mice; Molecular biology; Nitric oxide; Original; Original Article; Oxidative stress; Pressure dependence; Signal Transduction; Thorax; Umbilical vein; Veins & arteries; Yes-associated protein; Hypertension; Endothelial dysfunction; Oxidative stress; YAP; Galectin-3; Angiotensin II
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-022-04623-5

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.