The Role of the Pulmonary Vascular Microenvironment in Chronic Thromboembolic Pulmonary Hypertension

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by persistent obstruction and vascular remodeling of the pulmonary arteries following pulmonary thromboembolism (PTE), diagnosed after a minimum of 3 months of therapeutic anticoagulation. Disease progression from PTE to CTEPH takes place in the pulmonary circulation, where the vascular microenvironment is composed of a fluid portion that includes blood cells and components of the fibrinolytic system, and various vascular cells, including endothelial and smooth muscle cells. Following PTE, the homeostasis of the pulmonary vascular microenvironment is disrupted, leading to the accumulation of inflammatory mediators and immune cells at the site of thrombosis. Platelets are also involved in the regulation of coagulation and inflammation, and functional changes such as impaired fibrinolysis are observed. Subsequently, endothelial cell dysfunction and smooth muscle cell dysregulation lead to delayed thrombus resolution and pulmonary vascular remodeling, eventually resulting in CTEPH. Early intervention targeting the aberrant vascular microenvironment may thwart or mitigate the transition from PTE to CTEPH. Here, we discuss the development of CTEPH from the perspective of the pulmonary vascular microenvironment and examine its related biomarkers and therapeutic methods for CTEPH diagnosis and treatment.