New therapies in pulmonary arterial hypertension: Recent insights
Abstract
Pulmonary Arterial Hypertension (PAH) is a complex and progressive disease characterized by elevated pulmonary vascular resistance and right heart failure. Current therapies primarily focus on pulmonary vasodilation; however, novel approaches that target the underlying pathophysiological mechanisms-such as TGF-β signalling, epigenetic alterations, growth factors, inflammation, and extracellular matrix remodelling-are promising alternatives for improving treatment outcomes. This is a review of recent advances in the development of innovative therapeutic strategies for PAH. The first section of this paper explores approaches targeting TGF-β signalling, both acting directly on receptors through drugs like Sotatercept and exogenous BMP9, and indirectly, inhibiting the degradation of key receptors, such as BMPR2. Subsequent sections describe treatments that target epigenetic regulators, e.g. poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors and direct BRD4 antagonists, tyrosine kinase inhibitors (Seralutinib), and therapies aimed at inflammation, such as IL-6 inhibitors, CD-20 inhibitors, and monoclonal antibodies that prevent macrophage migration. Finally, strategies that target the serotonin pathway, and other metabolic and hormonal pathways are described. This review includes both preclinical and clinical trial data that support efficacy, safety and the future potential of such therapies. Collectively, these therapeutic approaches can be valuable in treating PAH by targeting…
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