Correlation between gene polymorphism of endothelial protein C receptor and cerebral infarction in Chinese Han population of Hubei province / 中国实验血液学杂志

In order to explore the distribution frequency of endothelial protein C receptor (EPCR) gene A6936G variant and to study the correlation between this mutation and cerebral infarction in Chinese Han population of Hubei province district. The genotype and allele frequencies of EPCR A6936G were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 380 cerebral infarction patients and 380 healthy Chinese Han persons. The results indicated that the frequencies of A/A, A/G and G/G genotypes in cerebral infarction group were 77.1%, 22.1% and 0.8% respectively. While the frequencies of A/A and A/G genotypes in control group were 88.2% and 11.8%, and without G/G genotype. It is concluded that A6936G polymorphism of EPCR can be detected in Chinese Han population of Hubei province district, which may be correlated with the increasing risk of thrombosis in cerebral infarction patients.

Effects of shear stress on protein C activation, EPCR expression and TM expression in endothelial cells / 生物医学工程学杂志

The protein C anticoagulant pathway plays a fundamental role in the control of coagulation system and inflammatory response. It has been well established that physiological levels of shear stress induce endothelial structural change and modulate gene and protein expression. However, the role of shear stress in protein C pathway remains unknown. In the present study, we evaluated the effect of shear stress on the activation of protein C as well as on the expression of endothelial protein C receptor (EPCR) and thrombomodulin (TM) in human umbilical vein endothelial cells (HUVECs) which were exposed to TNF-alpha alone, shear stress alone, and TNF-alpha under shear stress. We found: (1) Either TNF-alpha or shear stress alone significantly reduced EPCR expression and protein C activation in HUVECs; and simultaneous exposure of HUVECs to TNF-alpha and shear stress resulted in a further decrease of EPCR expression and protein C activation (P<0.05); (2) Simultaneous exposure of HUVECs to TNF-alpha and shear stress resulted in the increase of soluble EPCR level more significantly than did the exposure of HUVECs to either TNF-alpha or shear stress alone (P<0.05); (3) Shear stress significantly increased TM expression on HUVECs, whereas TNF-alpha inhibited TM expression; shear stress could strongly neutralize TNF-alpha's inhibitive effect on TM expression. We therefore conclude that shear stress may play an important role in protein C pathway, which may be fulfilled by regulating EPCR expression and TM expression in endothelial cells.

Activated protein C ameliorates TNF-alpha-induced inflammatory response of endothelium via the endothelial protein C receptor / 生物医学工程学杂志

It has been demonstrated that the activated protein C (APC) plays an important role in the inhibition of inflammation. The activation of protein C can be significantly enhanced by the endothelial cell protein C receptor (EPCR). Previous studies proposed that the APC regulates the inflammatory response in endothelial cells by suppressing the expression of adhesion molecules and the secretion of chemokines and cytokines. However, the precise mechanism of the inhibitory effect of APC on inflammation is still poorly understood. In the present study, we evaluated the anti-inflammatory effect of recombinant human APC (rhAPC) and whether its inhibitory effect is conducted through the EPCR-dependent mechanism on human umbilical vein endothelial cells (HUVECs). By exposing HUVECs to: (1) TNF-alpha; (2) rhAPC plus TNF-alpha; (3) anti EPCR antibody that prevents rhAPC interaction with EPCR; (4) TNF-alpha plus anti EPCR antibody; (5) rhAPC plus TNF-alpha in the presence of anti EPCR antibody, we found that APC was able to significantly inhibit the TNF-alpha-induced secretion of cytokines such as IL-1beta and IL-8, as well as the expression of adhesion molecules such as ICAM-1, VCAM-1 and E-selction in HUVECs. These results reveal a novel pathway by which APC protects endothelial cells from inflammatory mediators through an EPCR-dependent mechanism.