Cav-1 promotes atherosclerosis by activating JNK-associated signaling
- The First Affiliated Hospital of Dalian Medical University, 222 zhongshan Road, Dalian 116011 (China)
- The Second Affiliated Hospital of Dalian Medical University, 467 zhongshan Road, Dalian 116011 (China)
Highlights: • Cav-1 expression is up-regulated in endothelial cells of atherosclerotic lesions. • Cav-1 deficiency inhibits HFD-induced inflammation in ApoE–/– mice. • Cav-1 deletion is able to suppress HFD-induced oxidative stress and dyslipidemia in ApoE–/– mice. • JNK signaling is involved in Cav-1-modulated atherosclerosis. The objective of the study is to calculate the role and underlying the molecular mechanisms of caveolin-1 (Cav-1) in atherosclerosis (AS). Cav-1 was mainly expressed in the endothelial cells of atherosclerotic lesions in both human patients and apolipoprotein E deficient (ApoE{sup –/–}) mice. Cav-1 deficiency (Cav-1{sup –/–}) attenuated high-fat diet (HFD)-induced atherosclerotic lesions in ApoE{sup –/–} mice, supported by the reduced aortic plaques. Cav-1{sup –/–} reduced the macrophage content and decreased the release of inflammation-related cytokines or chemokine in serum or abdominal aortas, accompanied with the inactivation of inhibitor κB kinase κ (IKKβ)/p65/IκBα signaling pathway. Also, the activity of mitogen-activated protein kinases 7/c-Jun-N-terminal kinase (MKK7/JNK) signaling was decreased by Cav-1{sup –/–}. In addition, oxidative stress induced by HFD in ApoE{sup –/–} mice was alleviated by Cav-1{sup –/–}. In response to HFD, Cav-1{sup –/–} markedly reduced triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDLC) and very low-density lipoprotein-cholesterol (VLDLC) in serum of HFD-fed ApoE{sup –/–} mice, whereas enhanced high-density lipoprotein-cholesterol (HDLC) contents. Consistent with these findings, haematoxylin and eosin (H&E) and Oil Red O staining showed fewer lipid droplets in the liver of Cav-1-deficient mice. Further, real time-quantitative PCR (RT-qPCR) analysis indicated that Cav-1{sup –/–} alleviated dyslipidemia both in liver and abdominal aortas of ApoE{sup −/-} mice fed with HFD. Cav-1 inhibition-induced attenuation of inflammatory response, oxidative stress and dyslipidemia were confirmed in vitro using mouse vascular smooth muscle cells (VSMCs) treated with ox-LDL. Surprisingly, the processes regulated by Cav-1-knockdown could be abolished through promoting JNK activation in ox-LDL-treated VSMCs. In conclusion, Cav-1 expression could promote HFD-induced AS in a JNK-dependent manner.
- OSTI ID:
- 23105627
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 503, Issue 2; Other Information: Copyright (c) 2018 Published by Elsevier Inc.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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