Targeting heme oxygenase-1 in vascular disease.
Targeting heme oxygenase-1 in vascular disease.
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DOI：
10.2174/1389450111009011504
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发表时间：
2010-12
影响因子：
3.2
通讯作者：
Durante W
中科院分区：
文献类型：
--
作者：
Durante W
血红素加氧酶-1（HO-1）代谢血红素产生一氧化碳（CO）、胆绿素和铁。胆绿素随后通过胆绿素还原酶代谢为胆红素。HO-1是近年来发现的一个治疗血管疾病的靶点。HO-1的药理学诱导或基因转移改善动脉粥样硬化、血管成形术后再狭窄、静脉移植物狭窄、血栓形成、心肌梗死和高血压的动物模型中的血管功能障碍，而HO-1活性的抑制或基因缺失使这些病症恶化。HO-1提供的血管保护作用主要归因于其终产物：CO和胆色素、胆绿素和胆红素。这些终产物发挥有效的抗炎、抗氧化、抗凋亡和抗血栓形成作用。此外，CO和胆色素通过影响血管平滑肌细胞、内皮细胞、内皮祖细胞或白细胞的增殖、迁移和粘附来维持动脉损伤部位的血管稳态。目前正在开发几种策略来靶向血管疾病中的HO-1。通过血红素衍生物、膳食抗氧化剂或目前可用的药物药理学诱导HO-1是一种有前途的近期方法，而HO-1基因递送是一个长期的治疗目标。通过吸入或通过使用CO释放分子和/或CO增敏剂直接施用CO提供了靶向HO-1的有吸引力的替代方法。此外，单独或与CO组合的胆色素的递送提供了另一种预防血管疾病的途径。由于HO-1及其产物具有潜在的毒性，因此一个主要的挑战将是设计临床上有效的治疗方式，靶向HO-1而不引起任何不良反应。
Heme oxygenase-1 (HO-1) metabolizes heme to generate carbon monoxide (CO), biliverdin, and iron. Biliverdin is subsequently metabolized to bilirubin by biliverdin reductase. HO-1 has recently emerged as a promising therapeutic target in the treatment of vascular disease. Pharmacological induction or gene transfer of HO-1 ameliorates vascular dysfunction in animal models of atherosclerosis, post-angioplasty restenosis, vein graft stenosis, thrombosis, myocardial infarction, and hypertension, while inhibition of HO-1 activity or gene deletion exacerbates these disorders. The vasoprotection afforded by HO-1 is largely attributable to its end products: CO and the bile pigments, biliverdin and bilirubin. These end products exert potent anti-inflammatory, antioxidant, anti-apoptotic, and anti-thrombotic actions. In addition, CO and bile pigments act to preserve vascular homeostasis at sites of arterial injury by influencing the proliferation, migration, and adhesion of vascular smooth muscle cells, endothelial cells, endothelial progenitor cells, or leukocytes. Several strategies are currently being developed to target HO-1 in vascular disease. Pharmacological induction of HO-1 by heme derivatives, dietary antioxidants, or currently available drugs, is a promising near-term approach, while HO-1 gene delivery is a long-term therapeutic goal. Direct administration of CO via inhalation or through the use of CO-releasing molecules and/or CO-sensitizing agents provides an attractive alternative approach in targeting HO-1. Furthermore, delivery of bile pigments, either alone or in combination with CO, presents another avenue for protecting against vascular disease. Since HO-1 and its products are potentially toxic, a major challenge will be to devise clinically effective therapeutic modalities that target HO-1 without causing any adverse effects.
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影响因子：
6.2
作者：
Dellon, ES;Szczepiorkowski, ZM;Chung, RT
通讯作者：
Chung, RT
影响因子：
3.5
作者：
Aziz, M. Talaat Abdel;El-Asmer, Mohamed Farid;Mahfouz, Soheir
通讯作者：
Mahfouz, Soheir
影响因子：
20.1
作者：
Clark, JE;Naughton, P;Motterlini, R
通讯作者：
Motterlini, R
影响因子：
20.3
作者：
Bussolati, B;Ahmed, A;Mason, JC
通讯作者：
Mason, JC
影响因子：
15.9
作者：
Belcher, JD;Mahaseth, H;Vercellotti, GM
通讯作者：
Vercellotti, GM