The critical role of NFAT transcription factors in pulmonary arterial remodeling and pulmonary hypertension: from PASMC proliferation to therapeutic targeting.

Pulmonary vascular remodeling is the primary driver of pulmonary hypertension (PH) progression and represents a major therapeutic challenge. Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) is a key contributor to pulmonary vascular remodeling. Accumulating evidence indicates that activation of nuclear factor of activated T cells (NFAT) transcription factors plays a critical role in the phenotypic switching of PASMCs. This review outlines the involvement of the NFAT transcription factor family in PH pathogenesis. It details the regulatory pathways of NFAT1-5 in this process, particularly their functions in PASMC proliferation, synthesizes current findings on PH therapy by modulating NFAT activity, and discusses limitations of existing research to enhance understanding of the critical role of NFAT in PH. Collectively, current evidence suggests that activation of NFAT1-4 constitutes a fundamental molecular mechanism underlying aberrant PASMC proliferation, whereas the role of NFAT5 in PH remains to be further elucidated.