Update on novel targets and potential treatment avenues in pulmonary hypertension

Abstract

Pulmonary hypertension (PH) is a condition marked by a combination of constriction and remodeling within the pulmonary vasculature. It remains a disease without a cure, as current treatments were developed with a focus on vasodilatory properties but do not reverse the remodeling component. Numerous recent advances have been made in the understanding of cellular processes that drive pathologic remodeling in each layer of the vessel wall as well as the accompanying maladaptive changes in the right ventricle. In particular, the past few years have yielded much improved insight into the pathways that contribute to altered metabolism, mitochondrial function, and reactive oxygen species signaling and how these pathways promote the proproliferative, promigratory, and antiapoptotic phenotype of the vasculature during PH. Additionally, there have been significant advances in numerous other pathways linked to PH pathogenesis, such as sex hormones and perivascular inflammation. Novel insights into cellular pathology have suggested new avenues for the development of both biomarkers and therapies that will hopefully bring us closer to the elusive goal: a therapy leading to reversal of disease.

NTP42, a novel antagonist of the thromboxane receptor, attenuates experimentally induced pulmonary arterial hypertension

“…While the goals of current treatments are to achieve increased exercise capacity, improved quality of life, and to slow disease progression and lower mortality risk, none of the currently-approved therapies have been shown to slow pathological progression [25]. PAH remains an incurable condition with a high mortality rate, underscoring the need for new drugs to new therapeutic targets that will offer greater overall efficacy and tolerability/compliance [26].…”

Preventive treatment with ginsenoside Rb1 ameliorates monocrotaline-induced pulmonary arterial hypertension in rats and involves store-operated calcium entry inhibition

“…Pulmonary hypertension (PH), characterized by increased pulmonary vascular tone, vascular smooth muscle hyperplasia, and remodelling in distal pulmonary arteries, is a severe condition characterized by elevated pulmonary arterial pressure (PAP) that eventually leads to right heart failure and death (Huetsch et al 2016;Simonneau et al 2019). PH is divided into five categories according to cause, i.e., pulmonary arterial hypertension (PAH), PH due to left heart disease, PH due to lung disease and/or hypoxia, PH due to chronic blood clots in the lung and PH due to unknown causes (Simonneau et al 2019).…”

“…Pulmonary hypertension (PH), characterized by increased pulmonary vascular tone, vascular smooth muscle hyperplasia, and remodelling in distal pulmonary arteries, is a severe condition characterized by elevated pulmonary arterial pressure (PAP) that eventually leads to right heart failure and death (Huetsch et al. 2016 ; Simonneau et al. 2019 ).…”

A pro-con debate: current controversies in PAH pathogenesis at the American Thoracic Society International Conference in 2017

“…The debaters fought passionately with those in the audience, who were the final judges to declare debate winners. As we believe that this discourse is very much needed to advance our understanding of PAH pathogenesis and identify reliable and promising treatment targets (36,42), here, we summarize the main points and counterpoints for each topic to make them available to the broader community with the goal to stimulate further discussion and research. Each argument is prefaced by brief summary of the key points, which are subsequently elaborated in a concise narrative.…”