Wei Yingying, Wu Daiqin, Deng Na, Xu Fujia, Luo Sihan, Fan Xinxin, Guo Haijun, Chen Jingjing, Li Wei, Si Xiaoyun
Department of Cardiovascular Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Front Cardiovasc Med. 2025 Jul 9;12:1497938. doi: 10.3389/fcvm.2025.1497938. eCollection 2025.
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 post-transcriptional 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.
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.
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.
肺动脉高压（PAH）是一种进行性临床综合征，其特征为肺血管重塑和肺动脉压力升高，具有高发病率和死亡率。尽管靶向治疗改善了患者预后，但恢复正常血流动力学和逆转血管病变仍是未解决的挑战。异质性核糖核蛋白A2/B1（HNRNPA2B1）是一种参与mRNA加工和转录后调控的RNA结合蛋白，它调控包括细胞增殖、凋亡、血管生成和内皮稳态在内的关键过程。然而，其在PAH发病机制中的作用仍不清楚。本综述综合了目前关于HNRNPA2B1在PAH中的证据，评估其潜在的机制作用，并讨论治疗意义。鉴于PAH与HNRNPA2B1之间的许多联系都是推测性的，因此迫切需要进行严格的机制研究以阐明其病理生物学相关性。
新出现的临床前证据表明，在大鼠模型中，沉默HNRNPA2B1可减轻野百合碱（MCT）诱导的肺动脉高压（PH）。从机制上讲，HNRNPA2B1通过多个信号级联之间的相互作用和巨噬细胞极化动态来调节血管平滑肌细胞（VSMC）增殖，这两者都是肺血管重塑的核心。然而，临床可转化性仍不确定，因为尚无研究最终证实HNRNPA2B1是人类PAH的可成药靶点。
最近的证据表明，HNRNPA2B1已成为PAH的潜在治疗靶点。然而，进一步的研究对于阐明其在调节PAH潜在致病机制中的作用至关重要。
