title: Intraplaque injection of Ad5-CMV.p53 aggravates local  inflammation and leads to plaque instability in rabbits.
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-microl 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 (R(2) = 0.761, and R(2) = 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.
authors: 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.
authors: Lei
authors: L
authors: Zhang
authors: Department of Traditional Chinese Medicine, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China.
authors: Yan
authors: Y
authors: Liu
authors: Department of Traditional Chinese Medicine, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China.
authors: Xiao Ting
authors: XT
authors: Lu
authors: Department of Cardiology, Dongying People's Hspital, Shandong, P.R. China.
authors: Xin Sheng
authors: XS
authors: Xu
authors: Department of Traditional Chinese Medicine, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China.
authors: Yu Xia
authors: YX
authors: Zhao
authors: 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.
authors: Xiao Ping
authors: XP
authors: Ji
authors: 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.
authors: Peng Fei
authors: PF
authors: Zhang
authors: 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.
authors: Chun Xi
authors: CX
authors: Liu
authors: 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.
authors: Meng Xiong
authors: MX
authors: Tang
authors: 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.
authors: Wen Qiang
authors: WQ
authors: Chen
authors: 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.
authors: Yun
authors: Y
authors: Zhang
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D050197:Atherosclerosis / Q000473:pathology*; D003587:Cytomegalovirus / Q000235:genetics*; D016158:Genes, p53; D005822:Genetic Vectors; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology*; D008297:Male; D011817:Rabbits