C-reactive protein decreases expression of VEGF receptors and neuropilins and inhibits VEGF165-induced cell proliferation in human endothelial cells.
C-reactive protein (CRP) is associated with cardiovascular disease. However, its biological functions for the vascular system are largely unknown. The objective of this study was to determine whether CRP could affect endothelial cell proliferation and expression of VEGF receptors (VEGFRs) and/or neuropilins. Human coronary artery endothelial cells (HCAECs) treated with CRP showed a significant reduction of mRNA levels of VEGFR-2, VEGFR-3, NRP-1, and NRP-2 by 34%, 63%, 41%, and 43%, respectively, as compared to untreated control cells (p < 0.05) by real-time PCR analysis. In addition, VEGF165-induced cell proliferation was determined by [3H]thymidine incorporation and MTS assay as well as capillary-like tube formation on Matrigel. HCAECs pretreated with CRP significantly decreased VEGF165-induced [3H]thymidine incorporation by 73%, MTS absorbance by 44%, and capillary-like tube formation by 54% as compared to CRP-untreated cells (p < 0.05). These data demonstrate that CRP significantly attenuates VEGF165-induced HCAEC proliferation and capillary-like tube formation through downregulation of expression of VEGFRs and NRPs. This study suggests a new molecular mechanism underlying the adverse effect of CRP on the vascular system.
Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Hui
H
Yang
Bicheng
B
Nan
Shaoyu
S
Yan
Min
M
Li
Qizhi
Q
Yao
Changyi
C
Chen
D002097:C-Reactive Protein / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D039921:Neuropilins / Q000235:genetics*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000502:physiology
D039921:Neuropilins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D002097:C-Reactive Protein; D040262:Receptors, Vascular Endothelial Growth Factor