Prostaglandin E1 dose-dependently promotes stability of atherosclerotic plaque in a rabbit model

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Abstract:

This study evaluated the effect of prostaglandin E1 (PGE1) on the stability of atherosclerotic plaque. A vulnerable plaque model was established in rabbits, using balloon injury combined with a high-cholesterol diet. The rabbits were distributed into a control group, a low-dose PGE1 treatment group, a moderate-dose PGE1 treatment group, a high-dose PGE1 treatment group, and a simvastatin treatment group, with treatments lasting for 4 weeks. At week 13 (at the end of the experiments), atherosclerotic plaque was triggered by injection of Russell’s viper venom (Chinese) and histamine. Serological, pathological, immunohistochemical, and gene-expression studies were subsequently performed. PGE1 treatment did not alter serum lipid levels; however, PGE1 dose-dependently increased the thickness of the fibrous caps, and decreased the plaque vulnerability index. The plaque contents of macrophage- and the mRNA levels of monocyte-chemotactic protein-1, matrix metalloproteinase-1, and matrix metalloproteinase-9 were markedly reduced in all of the PGE1 treatment groups, with the high-dose of PGE1 being more effective than the simvastatin treatment. These findings suggest that PGE1 dose-dependently enhances the stability of atherosclerotic plaque. The high-dose of PGE1 presented more protection in terms of inhibiting macrophage accumulation and inflammatory expression in plaque. Our findings suggest a novel drug for the treatment of atherosclerosis.

Keywords: MMP-1; MMP-9; inflammation; macrophage; plaque vulnérable; prostaglandin E1; prostaglandine E1; simvastatin; simvastatine; vulnerable plaque

Document Type: Research Article

DOI: http://dx.doi.org/10.1139/y11-115

Affiliations: 1: Department of Clinical Pharmacy, School of Pharmacy, Shandong University, Jinan, Shandong 250012, P.R. China. 2: Geriatric Department, Qianfoshan Hospital of Shandong Province, Jinan, Shandong 250014, P.R. China. 3: Department of Pharmacy, Qianfoshan Hospital of Shandong Province, No. 16766 Jingshi Road, Jinan, Shandong 250014, P.R. China.

Publication date: February 20, 2012

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