Current and emerging therapeutic approaches to pulmonary hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a progressive and fatal lung disease of multifactorial etiology. Most of the available drugs and FDA-approved therapies for treating pulmonary hypertension attempt to overcome the imbalance between vasoactive and vasodilator mediators, and restore the endothelial cell function. Traditional medications for treating PAH include the prostacyclin analogs and receptor agonists, phosphodiesterase 5 inhibitors, endothelin-receptor antagonists, and cGMP activators. While the current FDA-approved drugs showed improvements in quality of life and hemodynamic parameters, they have shown only very limited beneficial effects on survival and disease progression. None of them offers a cure against PAH, and the median survival rate remains less than three years from diagnosis. Extensive research efforts have led to the emergence of innovative therapeutic approaches in the area of PAH. In this review, we provide an overview of the current FDA-approved therapies in PAH and discuss the associated clinical trials and reported-side effects. As recent studies have led to the emergence of innovative therapeutic approaches in the area of PAH, we also focus on the latest promising therapies in preclinical studies such as stem cell-based therapies, gene transfer, and epigenetic therapies.

Resveratrol Prevents Right Ventricle Dysfunction, Calcium Mishandling, and Energetic Failure via SIRT3 Stimulation in Pulmonary Arterial Hypertension

“…This study suggests that mitochondrial protection and cellular energetic preservation could be possible therapeutic targets to improve the PAH phenotype. The currently approved PAH medications decrease vascular remodeling by restoring the balance between vasoactive and vasodilator mediators [ 87 ]. However, researchers have begun to focus on mitochondrial disorders to develop new strategies.…”

Novel Experimental Therapies for Treatment of Pulmonary Arterial Hypertension

“…402 The use of the adenovirus vectors remains limited due to its strong inflammatory reaction associated with its gene transfer. 403 Advances in gene delivery technology have led to the development of new vectors with limited inflammatory reaction called adeno-associated virus (AAV). The use of such vectors is currently being used in experimental PH models.…”

Molecular and Genetic Profiling for Precision Medicines in Pulmonary Arterial Hypertension

“…PAH was initially described as a non-treatable disease. However, the recent advances in diagnostic tools, multi-omics technologies, and early treatment have significantly improved patients’ quality of life and overall life expectancy [ 15 , 16 , 17 ]. Current data shows that the median survival was 2.8 years between 1980 and 1991 when no specific and efficient treatments were available, while the median survival is 7–10 years in the modern treatment era [ 18 , 19 ].…”

“…Today, around 14 therapies are currently available and commonly used clinically. These therapies target three distinct pathways and aim to restore the balance between vasodilation and vasoconstriction [ 15 , 20 ]. The prostacyclin pathway and the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling potentiate vasodilation and attenuate the proliferation of vascular cells, including smooth muscle cells (SMCs) and endothelial cells (ECs) [ 21 ].…”