C‐reactive protein contributes to the hypercoagulable state in coronary artery disease

Abstract

Summary. Objectives: Elevated plasma C-reactive protein (CRP) levels predict coronary events, but it is unclear whether CRP plays a role in thrombosis associated with these events. We investigated tissue factor (TF) induction by CRP on peripheral blood mononuclear cells (PBMC) from patients with coronary disease. Patients and Methods: PBMC from 35 patients with stable angina (SA) in study 1, 10 male patients with SA, 10 with unstable angina (UA) and 10 matched controls in study 2, and 25 patients with inflammatory disorders (ID) and 24 normal controls in study 3 were stimulated with CRP, interferon-c (IFN) or lipopolysaccharide (LPS), or their combination. PBMC from additional normal donors were also stimulated with CRP in adherent and non-adherent conditions, and TF activity, antigen and mRNA expression detected. Results: CRP (5-25 lg mL )1 ) dose dependently induced more TF on PBMC from SA patients than 42 contemporary controls (P ¼ 0.001, study 1). Compared with controls, patients with SA or UA had higher basal, and much higher CRP-or CRP/LPS-induced monocyte TF activity although serum CRP levels were similar (study 2). IFN induced monocyte TF activity in patients with angina, but not in controls. Basal or CRP-induced TF levels did not differ between controls and ID, even though ID patients had much higher serum CRP levels (study 3). CRP-induced monocyte TF activity correlated with serum CRP levels in controls (P ¼ 0.005) and ID (P ¼ 0.007) in study 3, but not in patients with angina (P ¼0.84) in study 2. CRP induced more TF activity, protein and mRNA under adherent than nonadherent conditions implying that it may mainly target macrophages in lymphocyte-rich lesions. Conclusions: Our results indicate that monocytes from patients with angina are preactivated and express TF but CRP is unlikely to be a major priming factor in vivo. IFN and CRP further increase TF levels that may contribute to the hypercoagulable state in coronary disease.

Tissue Factor and Monocyte Chemoattractant Protein-1 Expression in Hypertensive Individuals with Normal or Increased Carotid Intima-Media Wall Thickness

“…Furthermore, CRP has been reported to promote monocyte chemotactic activity in response to MCP-1 via upregulation of monocyte CCR2 (35 ). By contrast, CRP had no effects in stimulating TF mRNA in highly purified monocytes from healthy patients (36 ) or angina patients (37 ), indicating that TF stimulation by CRP may be favored by the presence of other circulating cells and inflammatory mediators.…”

Upregulation of Monocyte Tissue Factor Activity Is Significantly Associated With Low-Grade Chronic Inflammation and Insulin Resistance in Patients With Metabolic Syndrome

“…15 In addition, we previously showed that monocytes from patients with unstable angina are preactivated and express TF. 12 Here, we have shown that PBMCs and monocytes from patients with MetS are more responsive to LPS than cells from normal subjects, thus suggesting that cells from MetS patients have undergone pre-activation. Therefore, pre-activated monocytes may infiltrate adipose tissue and contribute to the pathogenesis of inflammation and IR in patients with MetS.…”

“…We have also previously shown that TF antigen on monocytes from PBMCs can be detected by immunofluorescence. 12 Therefore, monocytes are the principle cells capable of TF synthesis. TF plays a significant role in both thrombosis and atherosclerosis.…”

Serum Amyloid A Induces Monocyte Tissue Factor

“…35). Earlier studies implicate CRP in induction of TF expression on blood monocytes (19,36,37), and because of the association of plasma CRP levels with increased risk of cardiovascular events in patients with unstable coronary syndromes, this suggested a prothrombotic role in the pathogenesis of atherosclerosis. Raised plasma levels of SAA are also associated with the pathogenesis of numerous chronic or recurrent inflammatory diseases, including amyloidosis, RA, and atherosclerosis (38,39).…”