PMID- 19602038 OWN - NLM STAT- MEDLINE DCOM- 20100719 LR - 20211020 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 13 IP - 8B DP - 2009 Aug TI - Intraplaque injection of Ad5-CMV.p53 aggravates local inflammation and leads to plaque instability in rabbits. PG - 2713-2723 LID - 10.1111/j.1582-4934.2008.00538.x [doi] AB - 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. FAU - Zhang, Lei AU - Zhang L AD - 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. FAU - Liu, Yan AU - Liu Y AD - Department of Traditional Chinese Medicine, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China. FAU - Lu, Xiao Ting AU - Lu XT AD - Department of Traditional Chinese Medicine, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China. FAU - Xu, Xin Sheng AU - Xu XS AD - Department of Cardiology, Dongying People's Hspital, Shandong, P.R. China. FAU - Zhao, Yu Xia AU - Zhao YX AD - Department of Traditional Chinese Medicine, Shandong University Qilu Hospital, Jinan, Shandong, P.R. China. FAU - Ji, Xiao Ping AU - Ji XP AD - 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. FAU - Zhang, Peng Fei AU - Zhang PF AD - 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. FAU - Liu, Chun Xi AU - Liu CX AD - 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. FAU - Tang, Meng Xiong AU - Tang MX AD - 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. FAU - Chen, Wen Qiang AU - Chen WQ AD - 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. FAU - Zhang, Yun AU - Zhang Y AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 SB - IM MH - Adenoviridae/*genetics MH - Animals MH - Atherosclerosis/*pathology MH - Cytomegalovirus/*genetics MH - *Genes, p53 MH - *Genetic Vectors MH - Immunohistochemistry MH - Inflammation/*etiology MH - Male MH - Rabbits PMC - PMC6512386 EDAT- 2009/07/16 09:00 MHDA- 2010/07/20 06:00 PMCR- 2009/08/01 CRDT- 2009/07/16 09:00 PHST- 2009/07/16 09:00 [entrez] PHST- 2009/07/16 09:00 [pubmed] PHST- 2010/07/20 06:00 [medline] PHST- 2009/08/01 00:00 [pmc-release] AID - JCMM538 [pii] AID - 10.1111/j.1582-4934.2008.00538.x [doi] PST - ppublish SO - J Cell Mol Med. 2009 Aug;13(8B):2713-2723. doi: 10.1111/j.1582-4934.2008.00538.x.