title: Perivascular adipose tissue-derived complement 3 is required for adventitial fibroblast functions and adventitial remodeling in deoxycorticosterone acetate-salt hypertensive rats.
abstract: OBJECTIVE
  To examine the role of perivascular adipose tissue (PVAT)-derived factors in the regulation of adventitial fibroblast (AF) function in vitro and in vivo.
  
  
  RESULTS
  PVAT is an active component of blood vessels. Bioactive substances released from PVAT play regulatory roles in vascular function. However, their effects on vascular AFs remain unclear. PVAT-conditioned medium stimulated AF migration using a transwell technique, and differentiation was evaluated by α-smooth muscle-actin induction. We identified the secretome of PVAT by liquid chromatography-tandem mass spectrometry. One of the major secretory proteins in PVAT is complement 3 (C3). The C3 antagonist and neutralizing antibody attenuated PVAT-conditioned medium-induced AF migration and differentiation. Similar to PVAT-conditioned medium, C3 recombinant protein stimulated AF migration and differentiation. We demonstrated that the effects of PVAT-derived C3 were mediated by the c-Jun N-terminal kinase pathway. Moreover, we found morphological changes in perivascular adipocytes and increased expression of C3 in PVAT that was tightly associated with adventitial thickening and myofibroblast clustering around PVAT in deoxycorticosterone acetate-salt hypertensive rats.
  
  
  CONCLUSIONS
  PVAT-derived C3 stimulated AF migration and differentiation via the c-Jun N-terminal kinase pathway. PVAT-derived C3 may contribute to adventitial remodeling in a deoxycorticosterone acetate-salt hypertensive model.
authors.affiliation: Laboratory of Vascular Biology and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Cheng-Chao
authors.initials: CC
authors.lastname: Ruan
authors.forename: Ding-Liang
authors.initials: DL
authors.lastname: Zhu
authors.forename: Qi-Zhi
authors.initials: QZ
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Shu-Jie
authors.initials: SJ
authors.lastname: Guo
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Li
authors.forename: Ping-Jin
authors.initials: PJ
authors.lastname: Gao
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002465:Cell Movement; D048430:Cell Shape; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D003176:Complement C3 / Q000378:metabolism*; D003238:Connective Tissue / Q000378:metabolism* / Q000473:pathology; D003470:Culture Media / Q000378:metabolism; D003900:Desoxycorticosterone / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006973:Hypertension / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D019899:Paracrine Communication; D040901:Proteomics / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation
chemical_list: D003176:Complement C3; D003470:Culture Media; D017673:Sodium Chloride, Dietary; D003900:Desoxycorticosterone; D048031:JNK Mitogen-Activated Protein Kinases