title: PEDF and PEDF-derived peptide 44mer stimulate cardiac triglyceride degradation via ATGL.
abstract: BACKGROUND
  Pigment epithelium-derived factor (PEDF) is a 50-kDa secreted glycoprotein that is highly expressed in cardiomyocytes. A variety of peptides derived from PEDF exerts diverse physiological activities including anti-angiogenesis, antivasopermeability, and neurotrophic activities. Recent studies demonstrated that segmental functional peptides of PEDF, 44mer peptide (Val78-Thr121), show similar neurotrophic and cytoprotective effect to that of the holoprotein. We found that PEDF can reduce infarct size and protect cardiac function after acute myocardial infarction (AMI). However, the effects of PEDF on cardiac triglyceride (TG) accumulation after AMI remain unknown. The present study was performed to demonstrate the influence of PEDF and its functional peptides 44mer on TG degradation in AMI.
  
  
  METHODS
  The left ascending coronary artery (LAD) was ligated to induce AMI. PEDF-small interfering RNA (siRNA)-lentivirus (PEDF-RNAi-LV) or PEDF-LV was delivered to the ischemic myocardium in order to knock down or overexpress PEDF, respectively. Oil Red O staining and a TG assay kit were used to analyze the TG content in cardiomyocytes and infarcted areas.
  
  
  RESULTS
  The TG content significantly decreased in the PEDF-overexpressing heart compared to the sham group (P < 0.05). Both rPEDF and 44mer administration stimulate the TG degradation in cultured cardiomyocytes (P < 0.05). Adipose triglyceride lipase (ATGL)-specific inhibitor, atglistatin, attenuated the PEDF or 44mer-induced TG lipolysis activation of cardiomyocytes at 10 μmol/L. The effects of PEDF and 44mer on myocardial TG degradation were also abolished when ATGL was downregulated.
  
  
  CONCLUSIONS
  We conclude that PEDF and 44mer promote TG degradation in cardiomyocytes after AMI via ATGL. The substitution of PEDF and 44mer may be a novel therapeutic strategy for cardiac TG accumulation after AMI.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. haozhang_xz@163.com.|Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221006, China. haozhang_xz@163.com.
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. sunteng00@126.com.
authors.forename: Teng
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221006, China. jxys139615@sina.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Research Facility Center for Morphology, Xuzhou Medical College, Xuzhou, 221004, China. hefengx@163.com.
authors.forename: Hongli
authors.initials: H
authors.lastname: Yu
authors.affiliation: Research Facility Center for Morphology, Xuzhou Medical College, Xuzhou, 221004, China. 18796248806@163.com.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221006, China. 15152117880@163.com.
authors.forename: Tengteng
authors.initials: T
authors.lastname: Wei
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221006, China. 365593850@qq.com.
authors.forename: Huazhu
authors.initials: H
authors.lastname: Cui
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: Research Facility Center for Morphology, Xuzhou Medical College, Xuzhou, 221004, China. gavinliu@xzmc.edu.cn.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. zhang_zhongming@xzmc.edu.cn.|Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221006, China. zhang_zhongming@xzmc.edu.cn.
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Research Facility Center for Morphology, Xuzhou Medical College, Xuzhou, 221004, China. dhy@xzmc.edu.cn.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Dong
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D015687:Cell Hypoxia; D005136:Eye Proteins / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism*; D066292:Lipid Droplets / Q000378:metabolism; D008066:Lipolysis; D008297:Male; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology; D017202:Myocardial Ischemia / Q000150:complications / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D009414:Nerve Growth Factors / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015843:Serpins / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D000217:Acyltransferases; D005136:Eye Proteins; D008049:Lipase; D009414:Nerve Growth Factors; D010455:Peptides; D012333:RNA, Messenger; D015843:Serpins; D014280:Triglycerides; D000099174:Pigment Epithelium-Derived Factor; C520594:Abhd5 protein, rat; C571275:PNPLA2 protein, rat