Background: Chronic kidney disease (CKD) is a major public health burden with high mortality. Vascular calcification(VC) is a critical pathological hallmark of CKD. Effective preventing and treating of VC are essential to reduce cardiovascular events in CKD patients. Recent studies have suggested a link between Yes-associated protein(YAP) and VC, but the underlying mechanisms remain poorly defined. Objective: To elucidate the molecular mechanisms by which YAP ameliorates VC and to identify novel therapeutic targets. Results: In a rat CKD model and in vascular smooth muscle cells (VSMCs) stimulated with high phosphate in vitro, YAP expression was markedly reduced. YAP overexpression ameliorated vascular wall injury, calcium salt deposition, and osteogenic transformation of VSMCs in CKD rats. Mechanistically, YAP bound to TRAF6 to promote Beclin1 ubiquitination, thereby disrupting Beclin1-Bcl2 interaction, enhancing autophagy, and suppressing VC. Conclusion: YAP attenuates CKD-associated VC by promoting VSMC autophagy through ubiquitination of Beclin1 and inhibition of its bingding to Bcl2.
[1]Shandong Univ, Qilu Hosp, Dept Cardiol, Jinan, Peoples R China.
[2]Chinese Minist Educ, Chinese Natl Hlth Commission, Key Lab Cardiovasc Remodeling & Funct Res, Jinan 250012, Shandong, Peoples R China.
[3]Chinese Acad Med Sci, Jinan 250012, Shandong, Peoples R China.
[4]Shandong Univ, Qilu Hosp, Natl Key Lab Innovat & Transformat Luobing Theory, Jinan, Peoples R China.
(8.0+极速模式)