Doxycycline stabilizes vulnerable plaque via inhibiting matrix metalloproteinases and attenuating inflammation in rabbits.

Autor: Mei Dong, Lin Zhong, Wen Qiang Chen, Xiao Ping Ji, Mei Zhang, Yu Xia Zhao, Li Li, Gui Hua Yao, Peng Fei Zhang, Cheng Zhang, Lei Zhang, Yun Zhang
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: PLoS ONE, Vol 7, Iss 6, p e39695 (2012)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0039695
Popis: Enhanced matrix metalloproteinases (MMPs) activity is implicated in the process of atherosclerotic plaque instability. We hypothesized that doxycycline, a broad MMPs inhibitor, was as effective as simvastatin in reducing the incidence of plaque disruption. Thirty rabbits underwent aortic balloon injury and were fed a high-fat diet for 20 weeks. At the end of week 8, the rabbits were divided into three groups for 12-week treatment: a doxycycline-treated group that received oral doxycycline at a dose of 10 mg/kg/d, a simvastatin-treated group that received oral simvastatin at a dose of 5 mg/kg/d, and a control group that received no treatment. At the end of week 20, pharmacological triggering was performed to induce plaque rupture. Biochemical, ultrasonographic, pathologic, immunohistochemical and mRNA expression studies were performed. The results showed that oral administration of doxycycline resulted in a significant increase in the thickness of the fibrous cap of the aortic plaque whereas there was a substantial reduction of MMPs expression, local and systemic inflammation, and aortic plaque vulnerability. The incidence of plaque rupture with either treatment (0% for both) was significantly lower than that for controls (56.0%, P
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