肺动脉高压形成中的血管重构分子生物学机制研究进展
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摘要
肺动脉高压(PAH)是以肺动脉压和肺血管阻力升高为特征的临床血流动力学症候群,可导致右心衰竭和死亡。血管重构是PAH最显著的组织病理学特征,其形成受多方面因素的调控。内质网应激、钙紊乱和线粒体功能紊乱通过调节细胞内钙稳态和细胞代谢调控血管细胞的增殖凋亡能力;表观遗传学现象(如DNA损伤和微小RNA表达异常)参与调控血管细胞的异常增殖;血管细胞表型转化(包括内皮细胞间质转化和平滑肌细胞表型转换)是引起血管细胞异常增殖的重要原因。血管重构由多种细胞和分子通路共同作用产生,针对多靶点来改善PAH中发生的异常血管重构,进而延缓甚至逆转PAH的进程,有望成为PAH治疗上新的突破口。
Pulmonary arterial hypertension(PAH) is a clinical hemodynamic syndrome characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance leading to right heart failure and death. Vascular remodeling is the most prominent histopathological feature of PAH, which is regulated by many factors.Endoplasmic reticulum stress, calcium disorder and mitochondrial dysfunction are involved in the vascular cell proliferation and apoptosis by regulating intracellular calcium homeostasis and cellular metabolism. Epigenetic phenomenon such as DNA damage and abnormal expression of miRNA are also involved in the regulation of abnormal proliferation of vascular cells. Vascular cell phenotype switching including endothelial-mesenchymal transition and smooth muscle cell phenotype switching play an important role in abnormal proliferation of vascular cells. Vascular remodeling is produced by a variety of cells and molecular pathways, and aiming at multiple targets which is expected to find a new breakthrough in the treatment of PAH,and to improve abnormal vascular remodeling, delay or even reverse the progression of PAH.
Pulmonary arterial hypertension(PAH) is a clinical hemodynamic syndrome characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance leading to right heart failure and death. Vascular remodeling is the most prominent histopathological feature of PAH, which is regulated by many factors.Endoplasmic reticulum stress, calcium disorder and mitochondrial dysfunction are involved in the vascular cell proliferation and apoptosis by regulating intracellular calcium homeostasis and cellular metabolism. Epigenetic phenomenon such as DNA damage and abnormal expression of miRNA are also involved in the regulation of abnormal proliferation of vascular cells. Vascular cell phenotype switching including endothelial-mesenchymal transition and smooth muscle cell phenotype switching play an important role in abnormal proliferation of vascular cells. Vascular remodeling is produced by a variety of cells and molecular pathways, and aiming at multiple targets which is expected to find a new breakthrough in the treatment of PAH,and to improve abnormal vascular remodeling, delay or even reverse the progression of PAH.
引文
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