HNRNPA2B1: A Novel Target in Pulmonary Arterial Hypertension

Yingying Wei¹Daiqin Wu²Na Deng¹Fujia Xu¹Sihan Luo¹Xinxin Fan¹Haijun Guo¹Jingjing Chen²Wei Li^2*Xiaoyun Si^2*

• ¹Guizhou Medical University, Guiyang, Guizhou Province, China
• ²Affiliated Hospital of Guizhou Medical University, Guiyang, China

Purpose of Review: Pulmonary arterial hypertension (PAH) is a progressive clinical syndrome characterized by pulmonary vascular remodeling and elevated pulmonary artery pressure, associated with high morbidity and mortality. While targeted therapies have improved patient prognosis, restoring normal hemodynamics and reversing vascular pathology remain unmet challenges. Heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1), an RNA-binding protein integral to mRNA processing and posttranscriptional regulation, governs critical processes including cell proliferation, apoptosis, angiogenesis, and endothelial homeostasis. However, its role in PAH pathogenesis remains poorly defined. This review synthesizes current evidence on HNRNPA2B1 in PAH, evaluates its potential mechanistic contributions, and discusses therapeutic implications. Given the fact that much of the connections between PAH and HNRNPA2B1 are speculative, rigorous mechanistic studies are imperative to clarify its pathobiological relevance.Recent Findings Emerging preclinical evidence suggests that HNRNPA2B1 silencing attenuates monocrotaline (MCT)-induced pulmonary hypertension (PH) in rat models. Mechanistically, HNRNPA2B1 modulates vascular smooth muscle cell (VSMC) proliferation via cross-talk between multiple signaling cascades and macrophage polarization dynamics, both central to pulmonary vascular remodeling. Nevertheless, clinical translatability remains uncertain, as no studies have yet conclusively validated HNRNPA2B1 as a druggable target in human PAH.Summary Recent evidence suggests HNRNPA2B1 has emerged as a potential therapeutic target for PAH.However, further studies are essential to elucidate its role in modulating the pathogenic mechanisms underlying PAH.