The role of mononuclear cell tissue factor and inflammatory cytokines in patients with chronic thromboembolic pulmonary hypertension

Abstract

Thrombosis and inflammation are two major factors underlying chronic thromboembolic pulmonary hypertension (CTEPH). Tissue factor (TF), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) may play critical roles in the process of CTEPH thrombosis and pulmonary vascular remodeling. Ten patients with a confirmed diagnosis of CTEPH, 20 patients with acute pulmonary thromboembolism and 15 patients with other types of pulmonary hypertension were enrolled in this study, along with 20 healthy subjects as the control group. The immunoturbidimetric method was used to determine the plasma content of CRP. The plasma levels of TNF-α, MCP-1, and TF antigen were measured by an enzyme-linked immunosorbent assay, and TF activity was measured by the chromogenic substrate method. Percoll density gradient centrifugation was used to separate peripheral blood mononuclear cells from plasma. The level of monocyte TF mRNA was examined by reverse transcriptase-polymerase chain reaction. The correlations between all indices described above were analyzed. In CTEPH patients, the expression of CRP, TNF-α, and MCP-1 was significantly higher than that in controls (P < 0.05). The levels of TF activity, TF antigen, and TF mRNA in monocyte cells were increased in CTEPH patients when compared with control subjects, but only the TF antigen and TF mRNA levels were significantly different (P < 0.05). In CTEPH patients, levels of CRP, MCP-1, and TNF-α significantly correlated with the level of TF antigen in plasma. TF gene expression was increased in patients with CTEPH, suggesting that blood-borne TF mainly comes from mononuclear cells. TF expression significantly correlated with levels of CRP, TNF-α and MCP-1. These factors may play an important role in the development of CTEPH via the inflammation–coagulation–thrombosis cycle.

Lack of T-bet reduces monocytic interleukin-12 formation and accelerates thrombus resolution in deep vein thrombosis

“…Delayed thrombus resolution is a clinical challenge that increases the risk of DVT recurrence and of post thrombotic syndrome, two conditions associated with high morbidity and increased risk of death 39 . Also pulmonary embolism 40 and chronic thromboembolic pulmonary hypertension 41 , 42 are characterized by strong thrombo-inflammatory responses and are potentially life threatening diseases, in which the inflammatory burden correlates with adverse outcomes. In the arena of atherosclerosis, coronary heart disease and atherothrombosis, the interrelationship between inflammation and adverse outcomes has been studied in much more detail 43 .…”

Platelet, monocyte and neutrophil activation and glucose tolerance in South African Mixed Ancestry individuals

“…CD142 initiates the extrinsic pathway of coagulation by activating Factor VII and plays a role in stimulating the activation of platelets and leucocytes and the release of pro-inflammatory cytokines2931. The expression of TF in type 2 diabetes however remains controversial.…”

The pathophysiology of chronic thromboembolic pulmonary hypertension

“…Other studies have described increased tissue factor gene expression [46], an increased frequency of mutations known to be associated with PAH [47] and differentially expressed microRNAs [48,49].…”