Ramakrishnan S, Anand Vidhu, Roy Sabita
Department of Pharmacology, University of Minnesota, Minneapolis, MN, 55455, USA,
J Neuroimmune Pharmacol. 2014 Mar;9(2):142-60. doi: 10.1007/s11481-014-9531-7. Epub 2014 Mar 9.
Infection, cancer and cardiovascular diseases are the major causes for morbidity and mortality in the United States according to the Center for Disease Control. The underlying etiology that contributes to the severity of these diseases is either hypoxia induced inflammation or inflammation resulting in hypoxia. Therefore, molecular mechanisms that regulate hypoxia-induced adaptive responses in cells are important areas of investigation. Oxygen availability is sensed by molecular switches which regulate synthesis and secretion of growth factors and inflammatory mediators. As a consequence, tissue microenvironment is altered by re-programming metabolic pathways, angiogenesis, vascular permeability, pH homeostasis to facilitate tissue remodeling. Hypoxia inducible factor (HIF) is the central mediator of hypoxic response. HIF regulates several hundred genes and vascular endothelial growth factor (VEGF) is one of the primary target genes. Understanding the regulation of HIF and its influence on inflammatory response offers unique opportunities for drug development to modulate inflammation and ischemia in pathological conditions.
根据疾病控制中心的数据，感染、癌症和心血管疾病是美国发病和死亡的主要原因。导致这些疾病严重程度的潜在病因要么是缺氧诱导的炎症，要么是炎症导致的缺氧。因此，调节细胞中缺氧诱导适应性反应的分子机制是重要的研究领域。分子开关可感知氧气供应情况，这些开关调节生长因子和炎症介质的合成与分泌。结果，通过重新编程代谢途径、血管生成、血管通透性、pH稳态来改变组织微环境，以促进组织重塑。缺氧诱导因子（HIF）是缺氧反应的核心介质。HIF调节数百个基因，血管内皮生长因子（VEGF）是主要靶基因之一。了解HIF的调节及其对炎症反应的影响为开发药物以调节病理状态下的炎症和缺血提供了独特的机会。
