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

Minxia Yang,Qiaoxian Zhang,Ningfang Lian,Zhihua Huang,Chaosheng Deng,Dawen Wu,Zhanghua Zhong,Kaixiong Liu,Xiaoting Lv

doi:10.1007/s11239-015-1323-2

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.

Highlights

Chronic thromboembolic pulmonary hypertension (CTEPH) is the consequence of thrombus resolution failure after the establishment of thrombosis within the elastic pulmonary arteries [1]
D-dimmer plasma concentrations were elevated in pulmonary thromboembolism (PTE), non-thromboembolic PH and chronic thromboembolic pulmonary hypertension (CTEPH) when compared with the control group, but only the difference between the PTE and control groups was statistically
In CTEPH patients, both C-reactive protein (CRP) (r = 0.92, P \ 0.01) and MCP1 (r = 0.66, P \ 0.05) levels significantly correlated with pulmonary artery systolic pressure, while tumor necrosis factor-a (TNF-a) levels did not (r = 0.49, P [ 0.05) (Fig. 2), suggesting that there is a link between CRP and monocyte chemoattractant protein 1 (MCP-1) and severity of disease in CTEPH

Summary

Introduction

Chronic thromboembolic pulmonary hypertension (CTEPH) is the consequence of thrombus resolution failure after the establishment of thrombosis within the elastic pulmonary arteries [1]. CTEPH is a common variation of pulmonary hypertension (PH) and is associated with significant morbidity and mortality [2, 3]. Historical data indicate that if left untreated, CTEPH is associated with a poor 5-year survival rate ranging from 10 to 40 % depending on the patient’s pulmonary hemodynamics [3, 4]. The treatment of CTEPH includes pulmonary thrombus endarterectomy (PEA), balloon angioplasty, and medical therapy. The outcome of PEA surgery is favorable,and its mortality rates less than 3–5 % [5]. Patients who are not candidates for surgery may benefit from PH-specific medical therapy [6].

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