Mehta Niyati U, Reddy Srinivasa T
aDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California, USA bDepartments of Medicine/Cardiology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Curr Opin Lipidol. 2015 Oct;26(5):384-7. doi: 10.1097/MOL.0000000000000208.
Hemoglobin and its scavenger proteins haptoglobin and hemopexin (Hx) associate with HDL and influence the inflammatory properties of HDL. Moreover, HDL from Hx-null mice is proinflammatory. In addition, Hx deficiency is implicated in a number of other inflammatory diseases such as septic shock and experimental autoimmune encephalomyelitis. This article highlights studies that demonstrate novel insights into the physiological protective role of Hx in inflammatory diseases.
Recent studies demonstrate that Hx-dependent uptake of extracellular heme leads to the deactivation of Bach1 repression leading to the transcriptional activation of antioxidant heme oxygenase-1 gene. Levels of circulating Hx have been implicated in the prognosis for patients with septic shock. In addition, Hx therapy has been shown to be beneficial in cardiovascular disease, cerebral ischemic injury, and experimental autoimmune encephalomyelitis.
These studies suggest that heme scavenging is a major mechanism by which Hx defends against oxidative stress and related inflammatory disorders. Hx therapy may provide a novel protective role against heme and oxidative stress-mediated inflammatory conditions including atherosclerosis.
血红蛋白及其清除蛋白结合珠蛋白和血红素结合蛋白（Hx）与高密度脂蛋白（HDL）相关联，并影响HDL的炎症特性。此外，来自Hx基因敲除小鼠的HDL具有促炎作用。另外，Hx缺乏与多种其他炎症性疾病有关，如脓毒症休克和实验性自身免疫性脑脊髓炎。本文重点介绍了一些研究，这些研究展示了对Hx在炎症性疾病中生理保护作用的新见解。
最近的研究表明，Hx依赖的细胞外血红素摄取导致Bach1抑制失活，从而导致抗氧化血红素加氧酶-1基因的转录激活。循环中Hx的水平与脓毒症休克患者的预后有关。此外，Hx疗法已被证明对心血管疾病、脑缺血损伤和实验性自身免疫性脑脊髓炎有益。
这些研究表明，血红素清除是Hx抵御氧化应激和相关炎症性疾病的主要机制。Hx疗法可能对包括动脉粥样硬化在内的血红素和氧化应激介导的炎症性疾病起到新的保护作用。
