One of the rarest and most complex group of diseases that affects the cardiopulmonary system is known as pulmonary hypertension (PH), a life-threatening clinical condition that in advanced stages eventually results in irreversible dysfunction of the right heart chamber and sudden cardiac death. Pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH) are two different groups within the PH clinical classification system, in which loss and obstructive remodeling of the lung vessels is responsible for a significant rise in pulmonary arterial (PA) pressure and pulmonary vascular resistance (PVR), resulting in a functional decline of the heart performance and progressive right ventricle (RV) failure.

PAH is a pre-capillary-type PH (Group 1), hemodynamically defined by a mean pulmonary arterial pressure (mPAP) >20 mmHg, PA wedge pressure ≤15 mmHg, and PVR ≥3 Wood units. Remodeling of pulmonary vessels in PAH is depicted by the accumulation of pulmonary artery smooth muscle (PASMCs) and endothelial cells (PAECs), fibroblasts, myofibroblasts, and pericytes in the PA walls. In addition, this remodeling process results in a loss of pre-capillary arteries and exacerbates perivascular inflammation. The excessive loss of PAECs is a key pathobiological feature of PAH. This phenomenon triggers the development of an apoptosis-resistant and hyperproliferative phenotype of PAECs. Subsequently, an intense proliferation of PAECs induces the formation of plexogenic lesions in the lung vessels, a histopathologic hallmark of PAH.

[…]