PEDF and PEDF-derived peptide 44mer stimulate cardiac triglyceride degradation via ATGL

• DOI: 10.1186/s12967-015-0432-1
• Publication Date: 2015-02-20T09:48:07Z
• Authors: Hao Zhang; Teng Sun; Xia Jiang; Hongli Yu; Meng Wang; Tengteng Wei; Huazhu Cui; Wei Zhuang; Zhiwei Liu; Zhongming Zhang; Hongyan Dong
• Keywords: Male; Lipolysis; Molecular Sequence Data; Myocardial Infarction; Myocardial Ischemia; Rats, Sprague-Dawley; 03 medical and health sciences; Animals; Myocytes, Cardiac; Amino Acid Sequence; Nerve Growth Factors; RNA, Messenger; Eye Proteins; Serpins; Triglycerides; Medicine(all); 0303 health sciences; Biochemistry, Genetics and Molecular Biology(all); Research; Myocardium; Lipase; Lipid Droplets; Cell Hypoxia; 3. Good health; Peptides; Acyltransferases

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.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.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.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.