Research Progress on the Regulation of Pulmonary Hypertension by the NOTCH3 Signaling Pathway

Pulmonary hypertension (PH) has a high lethality rate, severe low age of onset, unclear pathological mechanism, and limited efficacy of existing drugs. The NOTCH3 signaling pathway is an immediate communication that functions through ligand-receptor interactions, and has been widely investigated for its dual functionalities—acting as either an oncogenic factor or a tumor suppressor in various cellular microenvironments. Additionally, the NOTCH3 signaling cascade takes part in the pathophysiological processes and inflammatory mechanisms of cardiovascular disorders like PH, and its function in the occurrence and development of PH has attracted growing attention, with research having made notable advancements. These findings suggest that PH is closely associated with dysregulations in the NOTCH3 signaling transduction pathway. However, the mechanism of vascular remodeling in PH, biological function studies, and intervention strategies targeting NOTCH3 have not been well studied. Throughout this review, we center on presenting the origins of the NOTCH signaling pathway and summarize the involvement of the NOTCH3 signaling pathway in PH from multiple dimensions of vascular remodeling mechanisms and biological functions, with the objective of offering theoretical perspectives for in-depth understanding of the NOTCH3 signaling pathway and pharmaceutical research and development of PH-targeted therapeutics.