Endothelial C-reactive protein increases platelet adhesion under flow conditions

Abstract

While data regarding the pathogenetic role of C-reactive protein (CRP) in atherothrombosis are accumulating, it is still controversial whether local CRP secretion is of any pathobiological significance. The present study examined whether endothelial-derived CRP modulates autocrine prothrombotic activity. Endothelial cells were isolated from hearts of mice transgenic to human CRP and grown in primary cultures. Human CRP expression was confirmed in these cells compared with no expression in cultures derived from wild-type congenes. Adhesion of human platelets to endothelial cells was studied in the “cone and plate” flow system. Platelet adhesion to cells expressing CRP was significantly increased compared with that in controls ( n = 6, P < 0.01). The proadhesive effect of CRP was significantly suppressed in mouse heart endothelial cells and in human umbilical vein endothelial cells following treatment with small interfering RNA for human CRP. Adhesion was modulated by an increase in P-selectin. P-selectin expression correlated with a proadhesive phenotype, and blocking P-selectin with neutralizing antibody significantly decreased the adhesion of platelets to CRP-expressing cells (40.4 ± 10.5 to 9.4 ± 6.9 platelets/high-power field, n = 5 to 6, P < 0.01). In conclusion, human CRP that is locally produced in endothelial cells increases platelet adhesion to endothelial cells under normal shear flow conditions. These findings indicate that CRP exerts a local effect on endothelial cells via P-selectin expression, which promotes platelet adhesion and subsequent thrombus formation.

Electronegative Low-Density Lipoprotein Increases C-Reactive Protein Expression in Vascular Endothelial Cells through the LOX-1 Receptor

“…The L5-induced local secretion of CRP may contribute to endothelial cell damage by means of other mechanisms, as well. Grad and colleagues [43] reported that endothelial cells expressing CRP increase platelet adhesion to human endothelial cells. Furthermore, CRP has been shown to promote atherosclerosis formation by inducing endothelial cells to produce monocyte chemoattractant protein-1 [44] and to express cell adhesion molecules [45], [46].…”

Role of Vascular Inflammation in Coronary Artery Disease: Potential of Anti-inflammatory Drugs in the Prevention of Atherothrombosis

“…Besides being a marker of CAD, it seems that CRP plays a causative role in CAD and ACS. It has the ability to bind to phosphocholine to recognize some pathogens and the phospholipids of damaged cells [7]; it increases platelet adhesion to endothelial cells under normal shear flow conditions [15]; it can also activate the complement system and induce synthesis of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1) and E-selectin and inflammatory cytokines that could promote atherosclerosis and ACS [7,16]. In this way, it seems logical that drugs that are able to lowering CRP levels, such as proinflammatory cytokines, could reduce the progression of atherosclerosis and the incidence of ACS.…”

Platelet-Monocyte Aggregates and C-Reactive Protein are Associated with VTE in Older Surgical Patients

“…Interestingly, in experimental models, CRP promotes PMA formation and platelet adhesion to endothelial cells141516. Nevertheless, studies investigating whether circulating PMAs and CRP may mediate VTE in human thrombotic disease settings remain absent.…”