title: C-reactive protein can upregulate VEGF expression to promote ADSC-induced angiogenesis by activating HIF-1α via CD64/PI3k/Akt and MAPK/ERK signaling pathways.
abstract: Proliferation of the vasa vasorum has been implicated in the pathogenesis of atherosclerosis, and the vasa vasorum is closely associated with resident stem cells within the vasculature. C-reactive protein (CRP) is positively correlated with cardiovascular disease risk, and our previous study demonstrated that it induces inflammatory reactions of perivascular adipose tissue by targeting adipocytes.
  
  
  
  Here we investigated whether CRP affected the proliferation and proangiogenic paracrine activity of adipose-derived stem cells (ADSCs), which may contribute to vasa vasorum angiogenesis.
  
  
  
  We found that CRP did not affect ADSC apoptosis, cell cycle, or proliferation but did increase their migration by activating the PI3K/Akt pathway. Our results demonstrated that CRP can upregulate vascular endothelial growth factor-A (VEGF-A) expression by activating hypoxia inducible factor-1α (HIF-1α) in ADSCs, which significantly increased tube formation on Matrigel and functional vessels in the Matrigel plug angiogenesis assay. The inhibition of CRP-activated phosphorylation of ERK and Akt can suppress CRP-stimulated HIF-1α activation and VEGF-A expression. CRP can also stimulate proteolytic activity of matrix metalloproteinase-2 in ADSCs. Furthermore, CRP binds activating CD64 on ADSCs, rather than CD16/32.
  
  
  
  Our findings implicate that CRP might play a role in vasa vasorum growth by activating the proangiogenic activity of ADSCs.
authors.affiliation: Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China.|Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, 510120, People's Republic of China.|Laboratory of RNA and Major Disease of Brain and Heart, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China.
authors.forename: JiaYuan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China.|Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, 510120, People's Republic of China.|Laboratory of RNA and Major Disease of Brain and Heart, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China.
authors.forename: ZhenJie
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China.|Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, 510120, People's Republic of China.|Laboratory of RNA and Major Disease of Brain and Heart, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China.
authors.forename: MaoXiong
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China.|Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, 510120, People's Republic of China.|Laboratory of RNA and Major Disease of Brain and Heart, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China.|Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, 510120, People's Republic of China.|Laboratory of RNA and Major Disease of Brain and Heart, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China.
authors.forename: JianHua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Division of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.|Guangdong Province Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, Guangzhou, 510080, People's Republic of China.
authors.forename: JingSong
authors.initials: J
authors.lastname: Ou
authors.affiliation: Laboratory of RNA and Major Disease of Brain and Heart, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China.|Department of Anesthesiology, University of Virginia, Health Science Center, Charlottesville, VA, USA.
authors.forename: ZhiYi
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China. dr_wjf@hotmail.com.|Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, 510120, People's Republic of China. dr_wjf@hotmail.com.|Laboratory of RNA and Major Disease of Brain and Heart, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China. dr_wjf@hotmail.com.
authors.forename: JingFeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China. tjcyx1995@163.com.|Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, 510120, People's Republic of China. tjcyx1995@163.com.|Laboratory of RNA and Major Disease of Brain and Heart, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, People's Republic of China. tjcyx1995@163.com.
authors.forename: YangXin
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D019899:Paracrine Communication / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology; D014651:Vasa Vasorum / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017452:Receptors, IgG; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D002097:C-Reactive Protein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2
keywords: Adipose-deprived stem cell; Angiogenesis; C-reactive protein; Hypoxia-inducible factor-1α; Vascular endothelial growth factor