Novel Pharmacological Targets for Pulmonary Arterial Hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a rare disease characterized by an obliterative vasculopathy of the distal pulmonary circulation that results in severe elevation in pulmonary pressure and pulmonary vascular resistance. PAH is a progressive and devastating disease that usually results in right heart failure and death. Currently available medications have only moderate effects and none are curative. Thus, there is a pressing need for new pharmacologic approaches to this disease. In order to meaningfully advance the treatment of PAH, new agents must target the underlying cause of disease induction and progression. This review discusses the extensive work that has been done in the areas of altered glucose metabolism, tyrosine kinase inhibitions, signaling pathways associated with disease causing gene mutations such as the bone morphogenic protein receptor 2, and inflammation and immunomodulation including the effects of mesenchymal stem cells and the extracellular vesicles they secrete. Epigenetic modifications including the roles of micro RNAs, DNA methylation, histone acetylation and transcription factors that modulate pulmonary vascular remodeling are also reviewed. A brief background of each area of interest is provided with emphasis on those components that have potential to be exploited for the treatment of PAH. Significant findings of cell-based and animal studies and, where available, the results of early clinical trials, are presented to illustrate the potential of these novel therapeutic targets. Current challenges to the development of small peptides and biologicals for the treatment of PAH and direction for future studies are also briefly discussed.

The identification and verification of hub genes associated with pulmonary arterial hypertension using weighted gene co-expression network analysis

“…Pulmonary arterial hypertension (PAH) is a kind of severe cardiovascular disease, characterized by the progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, with complex etiology and poor prognosis, finally leading to right heart failure and death [ 1 ]. PAH is the term used to describe the finding of a mPAP ≥ 25 mmHg regardless of the underlying cause [ 2 ].…”

Association of risk assessment at diagnosis with healthcare resource utilization and health‐related quality of life outcomes in pulmonary arterial hypertension

“… 1 Group 1, pulmonary arterial hypertension (PAH), is a severe, chronic, and progressive form of PH characterized by pulmonary arterial remodeling that, untreated, results in right heart failure and death. 2 , 3 It is divided into subgroups based on underlying etiology. Idiopathic PAH (IPAH) occurs without a clear cause; additional forms include heritable PAH (HPAH), drug‐ and toxin‐induced PAH, and PAH associated with other medical conditions, including connective tissue disease (CTD), human immunodeficiency virus (HIV) infection, portal hypertension (PoPH), congenital heart disease (CHD), and schistosomiasis.…”