title: Dual gene transfer of bFGF and PDGF in a single plasmid for the treatment of myocardial infarction.
abstract: Basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) have been shown to be involved in a spectrum of cellular processes. In a previous study, we constructed a novel multigenic vector that contained two separate transcription units, each consisting of a strong promoter and an efficient polyadenylation signal. The two promoters were chosen for their ability to work simultaneously. Dual gene transfer of bFGF and PDGF in a single plasmid resulted in a significant increase in collateral blood vessel formation in a rabbit model of hind limb ischemia. The aim of the present study was to investigate the effect of this dual gene transfer strategy in a rat model of acute myocardial infarction (AMI). AMI was induced in rats by ligation of the left anterior descending coronary artery. The animals were randomly divided into four groups and treated with the following therapeutic strategies: Empty plasmid (control), plasmid encoding bFGF (PL-bFGF), plasmid encoding PDGF (PL-PDGF) or plasmid encoding bFGF and PDGF (PL-F-P). Echocardiography and histological examinations were performed 28 days subsequent to gene transfer. Dual gene therapy with bFGF and PDGF resulted in a significant angiogenic effect accompanied by vessel maturation, along with a significant reduction in infarct size and improvement in cardiac function. In a rat model of AMI, single plasmid-mediated dual gene therapy with bFGF and PDGF decreased infarct size and improved cardiac function due to the formation of functionally and morphologically mature vasculature. These results are relevant to the ongoing clinical trials involving the use of single plasmid-mediated angiogenic factors for the treatment of myocardial ischemic disease.
authors: Department of Cardiovascular Medicine, West China Hospital, Sichuan University, Sichuan 610041, P.R. China.
authors: Kaijun
authors: K
authors: Cui
authors: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, P.R. China.
authors: Xikun
authors: X
authors: Zhou
authors: Institute of Parasitic Disease Control and Prevention, Sichuan Center for Disease Control and Prevention, Chengdu, Sichuan 610041, P.R. China.
authors: Jingwen
authors: J
authors: Luo
authors: Department of Cardiovascular Medicine, West China Hospital, Sichuan University, Sichuan 610041, P.R. China.
authors: Jiayue
authors: J
authors: Feng
authors: Department of Cardiovascular Medicine, West China Hospital, Sichuan University, Sichuan 610041, P.R. China.
authors: Mingxia
authors: M
authors: Zheng
authors: Department of Cardiovascular Medicine, West China Hospital, Sichuan University, Sichuan 610041, P.R. China.
authors: Dejia
authors: D
authors: Huang
authors: Department of Cardiovascular Medicine, West China Hospital, Sichuan University, Sichuan 610041, P.R. China.
authors: Jian
authors: J
authors: Jiang
authors: Department of Cardiovascular Medicine, West China Hospital, Sichuan University, Sichuan 610041, P.R. China.
authors: Xiaoping
authors: X
authors: Chen
authors: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, P.R. China.
authors: Yuquan
authors: Y
authors: Wei
authors: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, P.R. China.
authors: Jiong
authors: J
authors: Li
authors: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, P.R. China.
authors: Li
authors: L
authors: Yang
keywords: acute myocardial infarction; basic fibroblast growth factor; platelet-derived growth factor