Back to Search
Start Over
Oxidized low-density lipoprotein induced hepatoma-derived growth factor upregulation mediates foam cell formation of cultured rat aortic vascular smooth muscle cells.
- Source :
-
European Journal of Cell Biology . Jun2021, Vol. 100 Issue 5/6, pN.PAG-N.PAG. 1p. - Publication Year :
- 2021
-
Abstract
- [Display omitted] • OxLDL exposure upregulates expression and release of HDGF in cultured aortic SMCs. • HDGF modulates atherogenic regulator expression and enhances oxLDL-induced foam cell formation in SMCs. • PI3K/Akt and MAPK activation is involved in oxLDL-induced HDGF, LOX-1, and CD36 upregulation. • HDGF gene silencing ameliorates oxLDL-induced atherogenic regulator upregulation and foam cell formation. • The oxLDL/LOX-1/HDGF axis may serve as a target for anti-atherogenesis. Vascular smooth muscle cells (SMCs) are important vascular components that are essential for the regulation of vascular functions during vascular atherosclerogenesis and vascular injury. Oxidized low-density lipoprotein (oxLDL) is known to induce SMC activation and foam cell transformation. This study characterized the role of hepatoma-derived growth factor (HDGF) in oxLDL-induced foam cell formation in cultured primary rat aortic SMCs. OxLDL exposure significantly increased HDGF expression and extracellular release. It also upregulated atherogenic regulators in SMCs, including TLR4, MyD88, LOX-1, and CD36. Exogenous HDGF stimulation not only increased the expression of cognate receptor nucleolin, but also the innate immunity regulators TLR4/MyD88 and lipid metabolism regulators, including LOX-1 and CD36. Oil red O staining showed that HDGF did not initiate, but enhanced oxLDL-driven foam cell formation in SMCs. Further signaling characterization demonstrated that oxLDL evoked activation of PI3K/Akt and p38 MAPK signaling pathways, both of which were involved in the upregulation of HDGF, LOX-1, and CD36 induced by oxLDL. Gene knockdown experiments using LOX-1 targeted siRNA demonstrated that LOX-1 expression was critical for oxLDL-induced HDGF upregulation, while HDGF gene depletion completely abolished oxLDL-triggered TLR4, LOX-1, and CD36 overexpression and foam cell formation in SMCs. These findings strongly suggest that oxLDL-induced HDGF upregulation participates in subsequent LOX-1 and CD36 expression in aortic SMCs and mechanistically contributes to the formation of SMC-derived foam cells. The oxLDL/LOX-1/HDGF axis may serve as a target for anti-atherogenesis therapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01719335
- Volume :
- 100
- Issue :
- 5/6
- Database :
- Academic Search Index
- Journal :
- European Journal of Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- 151884282
- Full Text :
- https://doi.org/10.1016/j.ejcb.2021.151169