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Atherosclerosis. 2009 Apr;203(2):360-70. doi: 10.1016/j.atherosclerosis.2008.05.059. Epub 2008 Jun 13.

Enhanced expression of vascular cell adhesion molecule-1 by corticotrophin-releasing hormone contributes to progression of atherosclerosis in LDL receptor-deficient mice.

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  • 1Department of Pharmacology, Nanjing Medical University, PR China.


Peripherally produced corticotrophin-releasing hormone (CRH) is a strong proinflammatory factor involved in many inflammatory diseases. However, to date, there is no evidence about the action of CRH on atherosclerosis, a chronic disease characterized by inflammatory reactions. In this study we observed the effect of CRH on atherosclerosis in low-density lipoprotein receptor-deficient (LDLr-/-) mice. Twelve-week-old, male LDLr-/- mice were subcutaneously injected with CRH (10microg/kg) or vehicle once a day for 8 weeks. The results indicated aortic atherosclerotic lesions were larger (P<0.01) in CRH-treated mice than those in untreated mice. CRH significantly up-regulated the expression of both protein and mRNA for vascular cell adhesion molecule-1 (VCAM-1), together with a markedly increased activation of nuclear factor kappa B (NF-kappaB) in aortas. In addition, the blood lipid levels were not influenced by CRH subcutaneous injection. The significant proatherogenic effect of CRH in LDLr-/- mice was largely attenuated by selective CRH receptor 1 (CRHR1) antagonist NBI27914 but not by specific CRH receptor 2 (CRHR2) antagonist antisauvagine-30 (anti-Svg-30). Meanwhile, both the enhanced expression of VCAM-1 and increased activation of NF-kappaB induced by CRH in aortas of LDLr-/- mice were also largely suppressed by NBI27914, whereas these inhibitory effects were not observed in anti-Svg-30 group. Taken together, these findings indicated that CRH may accelerate atherosclerosis progression in LDLr-/- mice via CRHR1. The enhanced VCAM-1 expression which probably resulted from increased activation of NF-kappaB induced by CRH, may be one of the important molecular mechanisms by which CRH accelerates atherosclerosis. This study provides a new insight into the effect of CRH on atherosclerosis and suggests a potential target for the prevention and treatment of atherosclerosis.

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