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PCSK9 induces endothelial cell autophagy by regulating the PI3K/ATK pathway in atherosclerotic coronary heart disease.
- Source :
-
Clinical hemorheology and microcirculation [Clin Hemorheol Microcirc] 2024 May 10. Date of Electronic Publication: 2024 May 10. - Publication Year :
- 2024
- Publisher :
- Ahead of Print
-
Abstract
- Objective: Atherosclerosis is a chronic inflammatory disease of the arteries, and its pathogenesis is related to endothelial dysfunction. It has been found that the protein convertase subtilin/kexin9 type (PCSK9) plays an important role in AS, but its specific mechanism is still unclear.<br />Methods: In this study, we first cultured human umbilical vein endothelial cells (HUVECs) with 50 or 100μg/ml oxidized low-density lipoprotein (ox-LDL) for 24 hours to establish a coronary atherosclerosis cell model.<br />Results: The results showed that ox-LDL induced HUVEC injury and autophagy and upregulated PCSK9 protein expression in HUVECs in a concentration-dependent manner. Silencing PCSK9 expression with siRNA inhibited ox-LDL-induced HUVEC endothelial dysfunction, inhibited the release of inflammatory factors, promoted HUVEC proliferation and inhibited apoptosis. In addition, ox-LDL increased the expression of LC3B-I and LC3B-II and decreased the expression of p62. However, these processes are reversed by sh-PCSK9. In addition, sh-PCSK9 can inhibit PI3K, AKT and mTOR phosphorylation and promote autophagy.<br />Conclusion: Taken together, our research shows that silencing PCSK9 inhibits the PI3K/ATK/mTOR pathway to activate ox-LDL-induced autophagy in vascular endothelial cells, alleviating endothelial cell injury and inflammation.
Details
- Language :
- English
- ISSN :
- 1875-8622
- Database :
- MEDLINE
- Journal :
- Clinical hemorheology and microcirculation
- Publication Type :
- Academic Journal
- Accession number :
- 38728182
- Full Text :
- https://doi.org/10.3233/CH-242172