Molecular Signature of a Right Heart Failure Program in Chronic Severe Pulmonary Hypertension
Molecular Signature of a Right Heart Failure Program in Chronic Severe Pulmonary Hypertension
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DOI：
10.1165/rcmb.2010-0412oc
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发表时间：
2011-12-01
影响因子：
6.4
通讯作者：
Natarajan, Ramesh
中科院分区：
文献类型：
--
作者：
Drake, Jennifer I.;Bogaard, Herman J.;Natarajan, Ramesh
右心衰竭是大多数严重肺动脉高压（PAH）患者的死亡原因，但人们对右心衰竭（RVF）的细胞和分子原因知之甚少。我们首先展示了正常大鼠右心室和左心室之间的差异基因表达模式，并假设存在区分 RVF 和适应性右心室肥厚 (RVH) 的分子右心衰竭程序，并且该程序在某些方面可能与左心力衰竭程序不同。通过微阵列和转录测序策略，我们使用两种适应性 RVH 模型来表征反映心肌结构生长和维持的基因表达模式。此外，两种RVF模型与纤维化、毛细血管稀疏、编码血管生成因子血管内皮生长因子、胰岛素样生长因子1、apelin和血管生成素-1的基因表达减少以及编码一组糖酵解酶的基因表达增加有关。用β-肾上腺素能受体阻滞剂治疗已形成的 RVF 可逆转 RVF，并部分逆转分子 RVF 程序。我们得出的结论是，正常的右心室和左心室在 mRNA 和 microRNA 的表达方面表现出明显可辨别的差异，并且 RVH 和 RVF 的特征在于与细胞生长、血管生成和能量代谢相关的不同基因表达模式。
Right heart failure is the cause of death of most patients with severe pulmonary arterial hypertensive (PAH) disorders, yet little is known about the cellular and molecular causes of right ventricular failure (RVF). We first showed a differential gene expression pattern between normal rat right and left ventricles, and postulated the existence of a molecular right heart failure program that distinguishes RVF from adaptive right ventricular hypertrophy (RVH), and that may differ in some respects from a left heart failure program. By means of microarrays and transcriptional sequencing strategies, we used two models of adaptive RVH to characterize a gene expression pattern reflective of growth and the maintenance of myocardial structure. Moreover, two models of RVF were associated with fibrosis, capillary rarefaction, the decreased expression of genes encoding the angiogenesis factors vascular endothelial growth factor, insulin-like growth factor 1, apelin, and angiopoeitin-1, and the increased expression of genes encodinga set of glycolytic enzymes. The treatment of established RVF with a beta-adrenergic receptor blocker reversed RVF, and partly reversed the molecular RVF program. We conclude that normal right and left ventricles demonstrate clearly discernable differences in the expression of mRNA and microRNA, and that RVH and RVF are characterized by distinct patterns of gene expression that relate to cell growth, angiogenesis, and energy metabolism.