Novel Molecular Mechanisms Involved in the Medical Treatment of Pulmonary Arterial Hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a severe condition with a high mortality rate despite advances in diagnostic and therapeutic strategies. In recent years, significant scientific progress has been made in the understanding of the underlying pathobiological mechanisms. Since current available treatments mainly target pulmonary vasodilation, but lack an effect on the pathological changes that develop in the pulmonary vasculature, there is need to develop novel therapeutic compounds aimed at antagonizing the pulmonary vascular remodeling. This review presents the main molecular mechanisms involved in the pathobiology of PAH, discusses the new molecular compounds currently being developed for the medical treatment of PAH and assesses their potential future role in the therapeutic algorithms of PAH.

Pulmonary Hypertension: Unveiling Molecular Mechanisms, Diagnosis, and Therapeutic Targets

“…Modifying BMPR-2 promoter methylation via drugs may be a therapeutic strategy. Another hypermethylated gene in PAH is ATP-binding cassette transporter A1 (ABCA1), which can be a biomarker for PAH risk [3,5,11].…”

“…Resveratrol, a SIRT-1 activator, can counteract these effects. SIRT-1 also influences mitochondrial metabolism and glycolytic shifts via HIF-1α regulation [3,5,11].…”

“…Imatinib, a tyrosine kinase inhibitor, may reverse PAH, but further trials are needed [12,20]. Targeting Src family kinases also holds therapeutic promise due to their involvement in ROS-induced vascular remodeling [5,6,13].…”

“…Pulmonary hypertension (PH) is a progressive and life-threatening disease characterized by increased pulmonary arterial pressure, which leads to right heart hypertrophy and eventually right heart failure [1][2][3][4][5]. Although the pathogenesis of PH is not yet fully understood, contemporary research illuminated the intricate molecular mechanisms involved in developing this disease and spurred advancements in diagnostic precision, uncovering innovative therapeutic avenues [3][4][5]. In this editorial, we delve into the multifaceted nature of PH, exploring its diverse manifestations, molecular mechanisms, and advances in therapeutic strategies.…”

Advances in Molecular and Translational Medicine

“…The article assesses the potential therapeutic value of these compounds in the management of PAH, including their mechanism of action, efficacy, and safety profile. The development of novel agents that can target pulmonary vascular remodeling may improve the prognosis of patients with PAH and provide a new treatment option for this challenging condition [14]. Atrial fibrillation (AF) is a common type of cardiac arrhythmia, and autoimmunity has been suggested to play a role in its development.…”