title: Pigment Epithelium-Derived Factor (PEDF) Improves Ischemic Cardiac Functional Reserve Through Decreasing Hypoxic Cardiomyocyte Contractility Through PEDF Receptor (PEDF-R).
abstract: Pigment epithelium-derived factor (PEDF), which belongs to the noninhibitory serpin family, has shown the ability to stimulate several physiological processes, such as antiangiogenesis, anti-inflammation, and antioxidation. In the present study, the effects of PEDF on contractility and calcium handling of rat ventricular myocytes were investigated.
  
  
  
  Adult Sprague-Dawley rat models of acute myocardial infarction (AMI) were surgically established. PEDF-lentivirus was delivered into the myocardium along and away from the infarction border to overexpress PEDF. Video edge detection was used to measure myocyte shortening in vitro. Intracellular Ca(2+) was measured in cells loaded with the Ca(2+) sensitive fluorescent indicator, Fura-2-acetoxymethyl ester. PEDF local overexpression enhanced cardiac functional reserve in AMI rats and reduced myocardial contracture bordering the infracted area. Exogenous PEDF treatment (10 nmol/L) caused a significant decrease in amplitudes of isoproterenol-stimulated myocyte shortening, Ca(2+) transients, and caffeine-evoked Ca(2+) transients in vitro. We then tested a potential role for PEDF receptor-mediated effects on upregulation of protein kinase C (PKC) and found evidence of signaling through the diacylglycerol/PKCα pathway. We also confirmed that pretreatment of cardiomyocytes with PEDF exhibited dephosphorylation of phospholamban at Ser(16), which could be attenuated with PKC inhibition.
  
  
  
  The results suggest that PEDF depresses myocyte contractility by suppressing phosphorylation of phospholamban and Ca(2+) transients in a PKCα-dependent manner through its receptor, PEDF receptor, therefore improving cardiac functional reserve during AMI.
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Lu
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Yi-Qian
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Li
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.affiliation: Research Center for Morphology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Liu
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Research Center for Morphology, Xuzhou Medical University, Xuzhou, Jiangsu, China zhang_zhongming@xzmc.edu.cn dhy@xzmc.edu.cn.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Dong
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China zhang_zhongming@xzmc.edu.cn dhy@xzmc.edu.cn.
authors.forename: Zhong-Ming
authors.initials: ZM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism / Q000502:physiology; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000502:physiology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D009200:Myocardial Contraction / Q000502:physiology*; D009203:Myocardial Infarction / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000502:physiology*; D009414:Nerve Growth Factors / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018013:Receptors, Neuropeptide / Q000502:physiology*; D015843:Serpins / Q000502:physiology*; D000099211:Phospholamban; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D002118:Calcium; D002135:Calcium-Binding Proteins; D005136:Eye Proteins; D009414:Nerve Growth Factors; D018013:Receptors, Neuropeptide; D015843:Serpins; D000099211:Phospholamban; D000099174:Pigment Epithelium-Derived Factor; C400531:pigment epithelium-derived factor receptor
keywords: cardiomyocyte; contractility; myocardial infarction; pigment epithelial‐derived factor; pigment epithelial‐derived factor receptor