• Open Access

Intraplaque injection of Ad5-CMV.p53 aggravates local inflammation and leads to plaque instability in rabbits

Authors

  • Lei Zhang,

    1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China
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    • These authors contributed to this work equally.

  • Yan Liu,

    1. Department of Traditional Chinese Medicine, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China
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    • These authors contributed to this work equally.

  • Xiao Ting Lu,

    Corresponding author
    1. Department of Traditional Chinese Medicine, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China
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  • Xin Sheng Xu,

    1. Department of Cardiology, Dongying People's Hspital, Shandong, P.R. China
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  • Yu Xia Zhao,

    1. Department of Traditional Chinese Medicine, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China
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  • Xiao Ping Ji,

    1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China
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  • Peng Fei Zhang,

    1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China
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  • Chun Xi Liu,

    1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China
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  • Meng Xiong Tang,

    1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China
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  • Wen Qiang Chen,

    1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China
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  • Yun Zhang

    Corresponding author
    1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China
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Correspondence to: Yun ZHANG, M.D., Ph.D,
Shandong University Qilu Hospital, Jinan, No.107, Wen Hua Xi Road, Jinan, Shandong, 250012, P.R. China.
Tel.: +86531-82169257
Fax: +86531-86169356
E-mail: zhangyun@sdu.edu.cn

Abstract

This study aims to develop a new animal model of vulnerable plaques and investigate the potential mechanisms of exogenous p53-induced plaque instability. Forty rabbits underwent aortic balloon injury, were fed a 1% cholesterol diet for 10 weeks and then normal chow for 6 weeks. Rabbits were divided into Ad5-CMV.p53-treated group (n= 16), Ad5-CMV.lac Z-treated group (n= 16) and blank control group (n= 8). Under the guidance of intravascular ultrasound, a 50-μl suspension of adenovirus containing p53 or lac Z was injected into the largest plaque of the first two groups, respectively, and these rabbits received pharmacological triggering 2 weeks later. In 76.9% of rabbits with p53 transfection, plaque rupture was found, which was significantly (P < 0.05) higher than that in the Ad5-CMV.lac Z-treated plaques (23.1%), or blank controls plaques (0%). Increased apoptotic cells, and subsequently, decreased vascular smooth muscle cells and collagen content, enhanced intima macrophage accumulation, increased C-reactive protein (CRP) and matrix metalloproteinases staining and high serum levels of high sensitive CRP (hs-CRP) and monocyte chemoattractant protein-1 (MCP-1) were observed in Ad5-CMV.p53-treated rabbits. However, a binary logistic regression model revealed that hs-CRP concentration rather than apoptosis rate played an independent role in plaque rupture with an odds ratio as 1.314 (95% CI: 1.041–1.657, P= 0.021), and there were high positive correlations between inflammatory biomarkers (hs-CRP or MCP-1) and apoptosis (R2= 0.761, and R2= 0.557, respectively, both P < 0.01). Intraplaque injection of p53 gene provides a safe and effective method for inducing plaque vulnerability in rabbits. The destabilizing effect of p53 overexpression is mediated mainly through apoptosis-enhanced inflammation rather than cell apoptosis itself.

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