The Roles of Hypoxia Signaling in the Pathogenesis of Cardiovascular Diseases.
The Roles of Hypoxia Signaling in the Pathogenesis of Cardiovascular Diseases.
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DOI：
10.5551/jat.rv17009
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发表时间：
2017-09-01
影响因子：
4.4
通讯作者：
Takeda N
中科院分区：
文献类型：
--
作者：
Abe H;Semba H;Takeda N
循环系统将血流分配到每个组织并输送氧气和营养物质。需要外周循环来维持每个组织中的生理功能。因此，循环障碍减少氧气输送，导致组织缺氧，这发生在几种心血管疾病中，包括动脉粥样硬化、肺动脉高压和心力衰竭。虽然心血管疾病可以诱导组织缺氧，但缺氧信号传导本身具有调节组织重塑过程或心血管疾病严重程度的潜力。缺氧诱导因子-1 α（HIF-1α）和HIF-2α是一类在转录水平上介导细胞缺氧反应的转录因子。我们和其他人已经报道了HIF-α信号在炎症的启动或调节中起着关键作用。HIF-α信号通路参与组织重塑过程，因此有可能成为治疗靶点。因此，阐明缺氧信号和组织重塑之间的分子联系将极大地帮助我们理解心血管疾病的病理生理学。本文就HIF-α在炎症过程中的作用，特别是在巨噬细胞中的作用作一综述。此外，缺氧信号的病理生理作用的心血管疾病的发展将进行讨论。
The circulatory system distributes blood flow to each tissue and transports oxygen and nutrients. Peripheral circulation is required to maintain the physiological function in each tissue. Disturbance of circulation, therefore, decreases oxygen delivery, leading to tissue hypoxia which takes place in several cardiovascular disorders including atherosclerosis, pulmonary arterial hypertension and heart failure. While tissue hypoxia can be induced because of cardiovascular disorders, hypoxia signaling itself has a potential to modulate tissue remodeling processes or the severity of the cardiovascular disorders. Hypoxia inducible factor-1α (HIF-1α) and HIF-2α belongs to a group of transcription factors which mediate most of the cellular responses to hypoxia at a transcriptional level. We, and others, have reported that HIF-α signaling plays a critical role in the initiation or the regulation of inflammation. HIF-α signaling contributes to the tissue remodeling processes; thus it has a potential to become a therapeutic target. Elucidation of the molecular link, therefore, between hypoxia signaling and tissue remodeling will greatly help us to understand the pathophysiology of the cardiovascular disorders. The purpose of this review is to give a brief overview of the current understanding about the function HIF-α in inflammation processes especially by focusing on its roles in macrophages. In addition, the pathophysiological roles of hypoxia signaling for the development of cardiovascular disease will be discussed.