Pulmonary Hypertension Research Group, Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Québec, Canada.
Pulm Circ. 2014 Jun;4(2):175-84. doi: 10.1086/675980.
Pulmonary arterial hypertension (PAH) is a vascular remodeling disease characterized primarily by increased proliferation and resistance to apoptosis in distal pulmonary arteries. Previous literature has demonstrated that the transcription factors NFAT (nuclear factor of activated T cells) and HIF-1α (hypoxia inducible factor 1α) are extensively involved in the pathogenesis of this disease and, more recently, has implicated STAT3 (signal transducer and activator of transcription 3) in their activation. Novel research shows that miR-204, a microRNA recently found to be notably downregulated through induction of PARP-1 (poly [ADP-ribose] polymerase 1) by excessive DNA damage in PAH, inhibits activation of STAT3. Contemporary research also indicates systemic impairment of skeletal muscle microcirculation in PAH and attributes this to a debilitated vascular endothelial growth factor pathway resulting from reduced miR-126 expression in endothelial cells. In this review, we focus on recent research implicating miR-204 and miR-126 in vascular remodeling processes, data that allow a better understanding of PAH molecular pathways and constitute a new hope for future therapy.
肺动脉高压（PAH）是一种血管重构疾病，其特征主要为远端肺动脉中细胞增殖增加和抗细胞凋亡能力增强。先前的文献表明，转录因子 NFAT（活化 T 细胞的核因子）和 HIF-1α（缺氧诱导因子 1α）广泛参与该疾病的发病机制，最近的研究表明 STAT3（信号转导和转录激活因子 3）也参与其激活。新的研究表明，miR-204 是一种 microRNA，最近发现其通过诱导 PARP-1（多聚 ADP-核糖聚合酶 1）的表达而显著下调，从而抑制了 STAT3 的激活。目前的研究还表明，PAH 中的骨骼肌微循环存在全身性损害，这归因于内皮细胞中 miR-126 表达减少导致血管内皮生长因子途径受损。在这篇综述中，我们重点介绍了最近涉及 miR-204 和 miR-126 在血管重构过程中的研究，这些数据有助于更好地理解 PAH 的分子途径，并为未来的治疗提供了新的希望。
