The Potential Application and Promising Role of Targeted Therapy in Pulmonary Arterial Hypertension

Meng Chien Willie Hsieh, Wei Ting Wang, Jwu Lai Yeh, Chuang Yu Lin, Yur Ren Kuo, Su Shin Lee, Ming Feng Hou, Yi Chia Wu*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

Pulmonary arterial hypertension (PAH) is a rare yet serious progressive disorder that is currently incurable. This female-predominant disease unfolds as a pan-vasculopathy that affects all layers of the vessel wall. Five classes of pharmacological agents currently exist to target the three major cellular signaling pathways identified in PAH but are incapable of effectively reversing the disease progression. While several targets have been identified for therapy, none of the current PAH specific therapies are curative and cost-effective as they fail to reverse vascular remodeling and do not address the cancer-like features of PAH. Our purpose is to review the current literature on the therapeutic management of PAH, as well as the molecular targets under consideration for therapy so as to shed light on the potential role and future promise of novel strategies in treating this high-mortality disease. This review study summarizes and discusses the potential therapeutic targets to be employed against PAH. In addition to the three major conventional pathways already used in PAH therapy, targeting PDGF/PDGFR signaling, regulators in glycolytic metabolism, PI3K/AKT pathways, mitochondrial heat shock protein 90 (HSP90), high-mobility group box-1 (HMGB1), and bromodomain and extra-terminal (BET) proteins by using their specific inhibitors, or a pharmacological induction of the p53 expression, could be attractive strategies for treating PAH.

Original languageEnglish
Article number1415
JournalBiomedicines
Volume10
Issue number6
DOIs
StatePublished - 06 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Warburg Effect
  • molecular base pathophysiology
  • pulmonary arterial hypertension
  • targeted therapy

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