Plasma monocyte chemoattractant protein-1 and pulmonary vascular resistance in chronic thromboembolic pulmonary hypertension

The pathogenesis of severe pulmonary hypertension seems to be related to in flammatory response in diseased sites. Monocyte chemoattractant protein-1 ( MCP-1) has been reported to play a role in the development of congestive he art failure. In this immunological response, activation and migration of le ukocytes including macrophages to the inflammatory region are important fac tors. We hypothesized that the severity of pulmonary hypertension may be re lated to MCP-1, which is thought to be upregulated by blood pressure or she ar stress in pulmonary vasculature as well as by immunological and inflamma tory reactions in chronic thromboembolic pulmonary hypertension (CTEPH). Ci rculating levels of MCP-1, interleukin-1 beta (IL-1 beta), and tumor necros is factor-alpha (TNF-alpha) were measured by sandwich ELISA in 14 patients with CTEPH. The plasma level of MCP-1 was significantly correlated with pul monary vascular resistance. In IL-1 beta and TNF-alpha, on the other hand, there was no correlation between cytokines and pulmonary hemodynamics. Path ological specimens obtained from the patients with CTEPH undergoing thrombo endarterectomy demonstrated immunoreactivity of MCP-1 in endothelium, smoot h muscle cells, and macrophages within neointima in the hypertensive large elastic pulmonary artery. We conclude that MCP-1 is upregulated in the remo deling of pulmonary arteries in close association with increased pulmonary vascular resistance in CTEPH.