期刊
AUTOPHAGY
卷 16, 期 6, 页码 1111-1129出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2019.1659613
关键词
Atherosclerosis; autophagy; CAV1; caveolin-1; caveolae associated protein 1; hyperglycemia; LDL transcytosis
类别
资金
- National Natural Science Foundation of China [81573432, 81373413, 81470458, 81570657]
- Ministry of Education of China [NCET-10-0409]
- Fundamental Research Funds for the Central Universities [2015ZHYX006, 2016YXZD023, 2016YXMS128]
- Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, HUST
Diabetes is a recognized high-risk factor for the development of atherosclerosis, in which macroautophagy/autophagy is emerging to play essential roles. The retention of low-density lipoprotein (LDL) particles in subendothelial space following transcytosis across the endothelium is the initial step of atherosclerosis. Here, we identified that high glucose could promote atherosclerosis by stimulating transcytosis of LDL. By inhibiting AMPK-MTOR-PIK3C3 pathway, high glucose suppresses the CAV-CAVIN-LC3B-mediated autophagic degradation of CAV1; therefore, more CAV1 is accumulated in the cytosol and utilized to form more caveolae in the cell membrane and facilitates the LDL transcytosis across endothelial cells. For a proof of concept, higher levels of lipids were accumulated in the subendothelial space of umbilical venous walls from pregnant women with gestational diabetes mellitus (GDM), compared to those of pregnant women without GDM. Our results reveal that high glucose stimulates LDL transcytosis by a novel CAV1-CAVIN1-LC3B signaling-mediated autophagic degradation pathway.
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