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CD137-CD137L Aggravates Calcification of Vascular Smooth Muscle Cell and Vasculature of ApoE−/− Mice Via Rab7-Mediated Autophagy.
- Source :
- Journal of Cardiovascular Translational Research; Dec2022, Vol. 15 Issue 6, p1297-1314, 18p
- Publication Year :
- 2022
-
Abstract
- Vascular calcification is an independent risk factor for acute cardiovascular events and a predictor of adverse prognosis; the abnormal fusion and degradation of autophagosomes and lysosomes are closely related to the calcification of VSMC and aortic AS plaque in ApoE<superscript>−/−</superscript> mice. Rab7 is a member of the Ras protein family and acts as a molecular switch in the fusion between autophagosomes and lysosomes. In this study, we found that the activation of the CD137-CD137L signal promoted calcification by inhibiting the expression and activity of Rab7, which regulates the degradation of autophagic cargo in vascular smooth muscle cells (VSMCs) and aortic atherosclerosis (AS) plaques in ApoE<superscript>−/−</superscript> mice. Knockdown of Rab7 impaired its tethering with the downstream molecule FYVE and coiled-coil containing 1 (FYCO1), which transports autophagosomes to lysosomes through microtubule motor kinesins and fuses with lysosomes to degrade the autophagic content. Overexpression of Rab7-alleviated calcification caused by the activation of the CD137 signaling pathway. In addition, FYCO1 knockdown promoted calcification even though the expression and activity of Rab7 were normal. Our results suggest that Rab7 is the target of CD137 signaling; Rab7 cannot interact with its downstream molecule FYCO1 when its activity and expression were inhibited by the activation of CD137 signaling pathway, thus inhibiting the autophagic degradation and promoting calcification. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19375387
- Volume :
- 15
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Journal of Cardiovascular Translational Research
- Publication Type :
- Academic Journal
- Accession number :
- 160579678
- Full Text :
- https://doi.org/10.1007/s12265-022-10272-7