Cross talk between autophagy and apoptosis in pulmonary hypertension.
Cross talk between autophagy and apoptosis in pulmonary hypertension.
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DOI：
10.4103/2045-8932.105029
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发表时间：
2012-10
影响因子：
2.6
通讯作者：
Choi AM
中科院分区：
文献类型：
--
作者：
Jin Y;Choi AM
内皮细胞（EC）凋亡和凋亡抵抗性增殖在肺动脉高压（PH）的发病机制中起重要作用。随后，EC损伤相关的平滑肌细胞（SMC）增殖促进血管重塑，并最终导致血管腔变窄、肺血管阻力增加、肺动脉压增加和右心衰竭。细胞死亡和增殖之间的不平衡发生在肺血管重塑和PH发病机制的每个阶段，并且涉及脉管系统中的每种细胞类型，包括但不限于EC、SMC和成纤维细胞。尽管有大量的研究，但关于内皮细胞从初始凋亡到抗凋亡增殖的细胞和分子机制仍不清楚。自噬是一种存在于几乎所有哺乳动物细胞中的保守而强大的调控机制，近年来的研究揭示了PH血管重塑过程中细胞命运的复杂而微妙的控制。在本文中，我们将讨论PH发病机制中细胞凋亡和自噬之间的相互作用如何调节细胞死亡或增殖的最新认识，特别是在涉及EC和SMC的肺血管重塑中。
Endothelial cell (EC) apoptosis and apoptosis resistant proliferation have been proposed to play crucial roles in the development of featured plexiform lesions in the pathogenesis of pulmonary hypertension (PH). Subsequently, EC injury associated smooth muscle cell (SMC) proliferation facilitates vascular remodeling and eventually leads to narrowed vascular lumen, increased pulmonary vascular resistance, increased pulmonary arterial pressure, and right heart failure. The imbalance between cell death and proliferation occurs in every stage of pulmonary vascular remodeling and pathogenesis of PH, and involves every cell type in the vasculature including, but not limited to ECs, SMCs, and fibroblasts. Despite extensive studies, the detailed cellular and molecular mechanisms on how the transition from initial apoptosis of ECs to apoptosis resistant proliferation on ECs and SMCs remains unclear. Recent knowledge on autophagy, a conservative and powerful regulatory machinery existing in almost all mammalian cells, has shed light on the complex and delicate control on cell fate in the development of vascular remodeling in PH. In this review, we will discuss the recent understandings on how the cross-talk between apoptosis and autophagy regulates cell death or proliferation in PH pathogenesis, particularly in pulmonary vascular remodeling involving ECs and SMCs.