title: C-reactive protein impairs angiogenic functions and decreases the secretion of arteriogenic chemo-cytokines in human endothelial progenitor cells.
abstract: C-reactive protein (CRP), a predictor of future cardiovascular diseases, has been reported to damage the vascular wall by inducing endothelial dysfunction and inflammation. This proatherogenic CRP was speculated to have a role in attenuating angiogenic functions of human endothelial progenitor cells (EPCs), possibly impairing vascular regeneration and increasing cardiovascular vulnerability to ischemic injury. Herein, we investigated the direct effect of CRP on angiogenic activity and gene expression in human EPCs. Incubation of EPCs with human recombinant CRP significantly inhibited EPC migration in response to vascular endothelial growth factor, possibly by decreasing the expression of endothelial nitric oxide synthase and subsequent nitric oxide production. In addition, CRP-treated EPCs showed the reduced adhesiveness onto an endothelial cell monolayer. When assayed for the gene expression of arteriogenic chemo-cytokines, CRP substantially decreased their expression levels in EPC, in part due to the upregulation of suppressors of cytokine signaling proteins. These results suggest that CRP directly attenuates the angiogenic and possibly arteriogenic functions of EPCs. This CRP-induced EPC dysfunction may impair the vascular regenerative capacity of EPCs, thereby leading to increased risk of cardiovascular diseases.
authors.affiliation: Department of Medicine, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Republic of Korea.
authors.forename: Wonhee
authors.initials: W
authors.lastname: Suh
authors.forename: Koung Li
authors.initials: KL
authors.lastname: Kim
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Young-Sam
authors.initials: YS
authors.lastname: Lee
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Jeong-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Hyung-Suk
authors.initials: HS
authors.lastname: Jang
authors.forename: In-Soon
authors.initials: IS
authors.lastname: Shin
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Lee
authors.forename: Jonghoe
authors.initials: J
authors.lastname: Byun
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Jeon
authors.forename: Duk-Kyung
authors.initials: DK
authors.lastname: Kim
mesh_terms: D001158:Arteries / Q000276:immunology / Q000502:physiology*; D002097:C-Reactive Protein / Q000494:pharmacology / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000037:antagonists & inhibitors*; D016207:Cytokines / Q000037:antagonists & inhibitors*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D011994:Recombinant Proteins / Q000494:pharmacology; D012038:Regeneration
chemical_list: D018925:Chemokines; D016207:Cytokines; D011994:Recombinant Proteins; D009569:Nitric Oxide; D002097:C-Reactive Protein; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III