title: PEDF improves cardiac function in rats with acute myocardial infarction via inhibiting vascular permeability and cardiomyocyte apoptosis.
abstract: Pigment epithelium-derived factor (PEDF) is a pleiotropic gene with anti-inflammatory, antioxidant and anti-angiogenic properties. However, recent reports about the effects of PEDF on cardiomyocytes are controversial, and it is not known whether and how PEDF acts to inhibit hypoxic or ischemic endothelial injury in the heart. In the present study, adult Sprague-Dawley rat models of acute myocardial infarction (AMI) were surgically established. PEDF-small interfering RNA (siRNA)-lentivirus (PEDF-RNAi-LV) or PEDF-LV was delivered into the myocardium along the infarct border to knockdown or overexpress PEDF, respectively. Vascular permeability, cardiomyocyte apoptosis, myocardial infarct size and animal cardiac function were analyzed. We also evaluated PEDF's effect on the suppression of the endothelial permeability and cardiomyocyte apoptosis under hypoxia in vitro. The results indicated that PEDF significantly suppressed the vascular permeability and inhibited hypoxia-induced endothelial permeability through PPARγ-dependent tight junction (TJ) production. PEDF protected cardiomyocytes against ischemia or hypoxia-induced cell apoptosis both in vivo and in vitro via preventing the activation of caspase-3. We also found that PEDF significantly reduced myocardial infarct size and enhanced cardiac function in rats with AMI. These data suggest that PEDF could protect cardiac function from ischemic injury, at least by means of reducing vascular permeability, cardiomyocyte apoptosis and myocardial infarct size.
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221006, China. zhanghao@xzmc.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221006, China. hefengx@163.com.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221006, China. 15152117880@163.com.
authors.forename: Shou-Jie
authors.initials: SJ
authors.lastname: Feng
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221006, China. 18796248806@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221006, China. sunteng00@126.com.
authors.forename: He-Xian
authors.initials: HX
authors.lastname: Shi
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221006, China. jxys139615@sina.com.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Chen
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221006, China. yuanguangda5157@163.com.
authors.forename: Guang-Da
authors.initials: GD
authors.lastname: Yuan
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221006, China. xiaofengshen1109@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Research Facility Center for Morphology, Xuzhou Medical College, Xuzhou 221004, China. redwolf07@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhuang
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221006, China. xuyizyq@163.com.
authors.forename: Yi-Qian
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221006, China. zhang_zhongming@xzmc.edu.cn.
authors.forename: Zhong-Ming
authors.initials: ZM
authors.lastname: Zhang
authors.affiliation: Research Facility Center for Morphology, Xuzhou Medical College, Xuzhou 221004, China. redwolf07@163.com.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis; D002199:Capillary Permeability; D015687:Cell Hypoxia; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor