C-reactive protein impairs angiogenic functions and decreases the secretion of arteriogenic chemo-cytokines in human endothelial progenitor cells.
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.
Suh
Wonhee
W
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.
Kim
Koung Li
KL
Choi
Jin-Ho
JH
Lee
Young-Sam
YS
Lee
Jae-Young
JY
Kim
Jeong-Min
JM
Jang
Hyung-Suk
HS
Shin
In-Soon
IS
Lee
Jung-Sun
JS
Byun
Jonghoe
J
Jeon
Eun-Seok
ES
Kim
Duk-Kyung
DK
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
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