HIF hydroxylase pathways in cardiovascular physiology and medicine.
HIF hydroxylase pathways in cardiovascular physiology and medicine.
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DOI：
10.1161/circresaha.117.305109
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发表时间：
2015-06-19
影响因子：
20.1
通讯作者：
Ratcliffe PJ
中科院分区：
文献类型：
--
作者：
Bishop T;Ratcliffe PJ
低氧诱导因子（HIF）是α/β异二聚体转录因子，其响应于氧可用性的变化而指导多种细胞和全身反应。氧敏感信号由一系列铁和2-酮戊二酸依赖性双加氧酶产生，所述双加氧酶催化HIF α亚基中特定脯氨酰和天冬酰胺酰残基的翻译后羟基化，从而促进它们在氧存在下的破坏和失活。在缺氧时，这些过程被抑制，允许HIF激活大量的转录级联反应。阐明这些途径开辟了心血管研究的几个新领域。在这里，我们回顾了HIF羟化酶途径在心脏发育和心血管控制中的作用。我们还考虑了在心血管疾病的治疗中治疗性调节HIF羟化酶的现状、机遇和挑战。
Hypoxia inducible factors (HIFs) are alpha/beta heterodimeric transcription factors that direct multiple cellular and systemic responses in response to changes in oxygen availability. The oxygen sensitive signal is generated by a series of iron and 2-oxoglutarate dependent dioxygenases that catalyse post-translational hydroxylation of specific prolyl and asparaginyl residues in HIFalpha subunits and thereby promote their destruction and inactivation in the presence of oxygen. In hypoxia, these processes are suppressed allowing HIF to activate a massive transcriptional cascade. Elucidation of these pathways has opened several new fields of cardiovascular research. Here we review the role of HIF hydroxylase pathways in cardiac development and in cardiovascular control. We also consider the current status, opportunities and challenges of therapeutic modulation of HIF hydroxylases in the therapy of cardiovascular disease.