C-reactive protein decreases expression of thrombomodulin and endothelial protein C receptor in human endothelial cells.
BACKGROUND
C-reactive protein (CRP) is associated with atherosclerosis and thrombosis. However, it is unclear whether CRP has direct effects on the antithrombogenic properties of endothelial cells. The objective of the present study was to determine the effect of CRP on the expression of thrombomodulin (TM) and the endothelial protein C receptor (EPCR) in human endothelial cells.


METHODS
Human coronary artery endothelial cells (HCAECs) were treated with CRP in a dose- and time-dependent manner. The messenger RNA levels of TM and EPCR were determined by real-time polymerase chain reaction. Anti-CD32 antibody and curcumin were used to block the potential effects of CRP.


RESULTS
In HCAECs, CRP (10 and 25 microg/mL) significantly reduced TM messenger RNA levels by 18 and 30%, respectively, compared with controls (P < .05). This effect was also confirmed in other types of human endothelial cells from umbilical veins and skin microvessels. The cells treated with CRP (10 and 25 microg/mL) showed significant reductions of EPCR mRNA levels by 34% and 33%, respectively (P < .05). Anti-CD32 antibody partially blocked CRP-induced downregulation of TM and EPCR in HCAECs. Furthermore, curcumin (5 and 10 microM) in combination with CRP (10 microg/mL) significantly increased TM mRNA levels by 45 and 100%, respectively, and increased EPCR mRNA levels by 24 and 45%, respectively, compared with those in CRP-treated cells (P < .05).


CONCLUSIONS
CRP significantly decreases the expression of TM and EPCR in human endothelial cells, thereby promoting thrombogenic conditions. This effect is partially mediated by CD32. Curcumin completely blocks CRP-induced downregulation of TM and EPCR in HCAECs.
Nan
Bicheng
B
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.
Yang
Hui
H
Yan
Shaoyu
S
Lin
Peter H
PH
Lumsden
Alan B
AB
Yao
Qizhi
Q
Chen
Changyi
C
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD; D001011:Aorta / Q000166:cytology; D002097:C-Reactive Protein / Q000494:pharmacology*; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology; D000074283:Endothelial Protein C Receptor; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D018180:Thrombomodulin / Q000235:genetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies; D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; D006023:Glycoproteins; C478370:PROCR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D018180:Thrombomodulin; D002097:C-Reactive Protein; D003474:Curcumin