Pathophysiology and new advances in pulmonary hypertension

Abstract

Pulmonary hypertension is a progressive and often fatal cardiopulmonary condition characterised by increased pulmonary arterial pressure, structural changes in the pulmonary circulation, and the formation of vaso-occlusive lesions. These changes lead to increased right ventricular afterload, which often progresses to maladaptive right ventricular remodelling and eventually death. Pulmonary arterial hypertension represents one of the most severe and best studied types of pulmonary hypertension and is consistently targeted by drug treatments. The underlying molecular pathogenesis of pulmonary hypertension is a complex and multifactorial process, but can be characterised by several hallmarks: inflammation, impaired angiogenesis, metabolic alterations, genetic or epigenetic abnormalities, influence of sex and sex hormones, and abnormalities in the right ventricle. Current treatments for pulmonary arterial hypertension and some other types of pulmonary hypertension target pathways involved in the control of pulmonary vascular tone and proliferation; however, these treatments have limited efficacy on patient outcomes. This review describes key features of pulmonary hypertension, discusses current and emerging therapeutic interventions, and points to future directions for research and patient care. Because most progress in the specialty has been made in pulmonary arterial hypertension, this review focuses on this type of pulmonary hypertension. The review highlights key pathophysiological concepts and emerging therapeutic directions, targeting inflammation, cellular metabolism, genetics and epigenetics, sex hormone signalling, bone morphogenetic protein signalling, and inhibition of tyrosine kinase receptors.

Polo-like kinase 1 promotes pulmonary hypertension

“…As the pulmonary branches and junctions are destroyed, the surface area of alveoli for gas exchange would be reduced [ 56 ]. This can ultimately lead to increased right ventricular afterload and the development of pulmonary hypertension [ 57 ]. Angiograms showed blunting of the pulmonary vasculature with absence of peripheral artery filling in WT mice.…”

The prevalence of pulmonary hypertension in post-tuberculosis and active tuberculosis populations: a systematic review and meta-analysis

“…Post-TB PH may share several pathophysiological mechanisms with other PH-chronic lung diseases and, additionally, may have several alternative pathophysiological pathways relating to other PH groups. Extensive post-TB lung damage, destruction of the pulmonary bed with reduced cross-sectional area of the pulmonary vasculature and hypoxic-induced vascular remodelling leading to the subsequent development of PH are the most cited mechanisms [ 11 , 12 ]. Additionally, TB directly affects the pulmonary vasculature, causing a vasculitis and endarteritis obliterans and may be associated with the development of chronic thromboembolic PH.…”

Expression and regulation of HIF-1a in hypoxic pulmonary hypertension: Focus on pathological mechanism and Pharmacological Treatment

“…ROS acts as a signaling molecule to activate HIF-1α and voltage gated calcium channel, and inhibit the expression of voltage gated potassium channel, which leads to an increase in intracellular concentration of Ca 2+ , and the contraction of smooth muscle cells 13 . Moreover, under continuous hypoxia, Rho kinase can be activated, and pulmonary vasoconstriction and HIF-1α expression can be enhanced 14 . However, under hypoxic stimulation, HIF-1a promotes an increase in the concentration of Ca 2+ in PASMC.…”