Probucol Attenuates Inflammation and Increases Stability of Vulnerable Atherosclerotic Plaques in Rabbits

Probucol Attenuates Inflammation and Increases Stability of Vulnerable Atherosclerotic Plaques in Rabbits

TINGTING LI,¹ WENQIANG CHEN,¹ FENGSHUANG AN,¹ HONGBO TIAN,² JIANNING ZHANG,³ JIE PENG,¹ YUN ZHANG¹ and YUAN GUO¹

¹The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Jinan, P.R. China
²Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, P.R. China
³Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, P.R. China

Probucol, a lipid-lowering agent with anti-oxidant properties, has been implicated in protection against atherogenesis, whereas its effect on plaques stability remains to be fully elucidated. The present study was aimed to test the hypothesis that probucol may attenuate inflammation and increase stability of vulnerable atherosclerotic plaques using a rabbit model. After abdominal aortic balloon injury, 45 rabbits were fed a 1% cholesterol diet for 24 weeks. From week 12 to week 24, the animals were treated with probucol (1% by weight in the diet), simvastatin (5 mg·kg^-1, positive control) or no drugs (control), respectively. At the end of week 22, recombinant-p53 adenovirus was injected into the abdominal aortic plaques. Two weeks later, plaque disruption was induced by injection of Chinese Russell's viper venom and histamine. The results showed that the incidence of plaque disruption in probucol or simvastatin groups was significantly lower than that in the control group (7.15% or 14.29% vs. 71.43% respectively, both P < 0.01). Probucol significantly increased the thickness of fibrous caps and decreased plaque vulnerability index. Serum concentrations of inflammatory cytokines and matrix metalloproteinases, and expression levels of Toll-like receptor (TLR)-2, TLR-4, monocyte chemoattractant protein-1, intercellular adhesion molecule 1, scavenger receptor A, CD36 and oxidized low-density lipoprotein receptor 1 within the lesions were markedly lower in both treatment groups than in the control group. We conclude that probucol increases the stability of vulnerable plaques, possibly through its lipid lowering, anti-inflammation and scavenger receptors suppression effects, suggesting probucol as a promising pharmacologic approach to stabilize vulnerable plaques.

keywords —— Atherosclerosis; inflammation; probucol; ultrasonography; vulnerable plaque

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Tohoku J. Exp. Med., 2011, 225, 23-34

Correspondence: Yuan Guo, Department of Cardiology, Qilu Hospital of Shandong University, No.107 Wenhua West Road, Jinan, Shandong, 250012, P.R. China.

e-mail: guoyuan9092@163.com