title: Pigment epithelium-derived factor promotes Fas-induced cardiomyocyte apoptosis via its receptor phospholipase A2.
abstract: OBJECTIVE
  Cardiovascular diseases cause significant morbidity and mortality worldwide. Recently, our research team demonstrated that a multifunctional cytokine, pigment epithelium-derived factor (PEDF), plays a critical role in regulating myocardial infarction. However, few researchers have studied the molecular mechanisms by which PEDF and its receptors influence the pathophysiology of cardiovascular disease. We tested the hypothesis that PEDF affects cardiomyocyte apoptosis under hypoxic conditions and determined the role that its receptors phospholipase A2 (PLA2) and laminin receptor play in this process.
  
  
  METHODS
  Cardiomyocytes were isolated from neonatal mice and treated with PEDF under normoxic and hypoxic conditions; then, apoptosis was assessed using Annexin V/PI staining and flow cytometry. Western blotting and immunofluorescence staining were used to detect PEDF receptor expression, and siRNA knockdown of PEDF receptors was performed to determine which receptor was involved in mediating cardiomyocyte apoptosis.
  
  
  RESULTS
  Our results demonstrated that PEDF increased cardiomyocyte apoptosis during hypoxia via Fas and that PEDF receptors were expressed on cardiomyocyte cell membranes. Furthermore, siRNA experiments indicated that the PEDF receptor PLA2 was responsible for inducing cardiomyocyte apoptosis via the Fas pathway.
  
  
  CONCLUSIONS
  PEDF promoted Fas-induced cardiomyocyte apoptosis via its receptor PLA2.
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, No. 172 West Changle Rd, Xi'an 710032, China.
authors.forename: Ji-ke
authors.initials: JK
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, No. 172 West Changle Rd, Xi'an 710032, China.
authors.forename: Hong-liang
authors.initials: HL
authors.lastname: Liang
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, No. 172 West Changle Rd, Xi'an 710032, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, No. 172 West Changle Rd, Xi'an 710032, China.
authors.forename: Chun-hu
authors.initials: CH
authors.lastname: Gu
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, No. 172 West Changle Rd, Xi'an 710032, China. Electronic address: yidh@fmmu.edu.cn.
authors.forename: Ding-hua
authors.initials: DH
authors.lastname: Yi
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, No. 172 West Changle Rd, Xi'an 710032, China; Department of Physiology, Fourth Military Medical University, No. 169 West Changle Rd, Xi'an, 710032, China. Electronic address: jmpei8@fmmu.edu.cn.
authors.forename: Jian-ming
authors.initials: JM
authors.lastname: Pei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002478:Cells, Cultured; D005136:Eye Proteins / Q000494:pharmacology*; D053222:Fas Ligand Protein / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D054507:Receptors, Phospholipase A2 / Q000378:metabolism*; D015843:Serpins / Q000494:pharmacology*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D053222:Fas Ligand Protein; D009414:Nerve Growth Factors; D054507:Receptors, Phospholipase A2; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor
keywords: Apoptosis; Cardiomyocyte; Fas; Phospholipase A(2); Pigment epithelium-derived factor