Hypoxamirs in Pulmonary Hypertension: Breathing New Life into Pulmonary Vascular Research.
Hypoxamirs in Pulmonary Hypertension: Breathing New Life into Pulmonary Vascular Research.
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DOI：
10.3978/j.issn.2223-3652.2012.08.01
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发表时间：
2012-09
影响因子：
2.4
通讯作者：
Chan SY
中科院分区：
文献类型：
--
作者：
Hale AE;White K;Chan SY
在哺乳动物细胞中，缺氧或氧可用性不足调节一组特定的microRNA的表达，这些microRNA以前被称为“hypoxamirs”。在过去的五年中，hypoxamir在调节细胞对缺氧的适应方面的重要性的认识急剧增长。在细胞水平上，每种hypoxamir可以同时调节多个（>100个）靶基因的表达，以控制基本的生物过程，包括存活、增殖、血管生成、迁移和代谢等。这些缺氧表型的适应不良失衡通常驱动许多缺血性心血管疾病，例如肺动脉高压-一种神秘的血管疾病，其特征在于继发于多种上游病因的明显和严重的全血管病变，特别是包括缺氧。然而，尽管缺氧细胞表型和疾病之间存在这种致病关系，但hypoxamir在调节肺动脉高压中的机制作用在很大程度上仍未被认识。已经取得了一些进展，探索特定的hypoxamirs在肺动脉高压的发展和进展的已知贡献，以及讨论潜在的方法，更全面地研究他们在这个复杂的疾病中的作用。因此，对它们在发病机制中的普遍作用的更复杂的理解可以为肺动脉高压的独特诊断和治疗策略奠定基础。
In mammalian cells, hypoxia, or inadequate oxygen availability, regulates the expression of a specific set of microRNA, which have been previously termed “hypoxamirs.” Over the past five years, the appreciation of the importance of hypoxamirs in regulating the cellular adaptation to hypoxia has grown dramatically. At a cellular level, each hypoxamir can simultaneously regulate expression of multiple (>100) target genes in order to control fundamental biological processes, including survival, proliferation, angiogenesis, migration, and metabolism, among others. A maladaptive imbalance of these hypoxic phenotypes often drives many ischemic cardiovascular diseases, such as pulmonary hypertension -- an enigmatic vascular disorder characterized by pronounced and severe panvasculopathy secondary to diverse upstream etiologies, notably including hypoxia. Yet, despite this pathogenic relationship between hypoxic cell phenotypes and disease, the mechanistic roles of hypoxamirs in modulating pulmonary hypertension remain largely unrecognized. Some advances have been made to explore the known contributions of specific hypoxamirs in the development and progression of pulmonary hypertension as well as discuss potential methods to more comprehensively study their roles in this complex disease. As a result, a more sophisticated understanding of their pervasive roles in pathogenesis could set the stage for unique diagnostic and therapeutic strategies in pulmonary hypertension.