Heme Oxygenase-1 and Carbon Monoxide in the Heart: The Balancing Act Between Danger Signaling and Pro-Survival.

Heme Oxygenase-1 and Carbon Monoxide in the Heart: The Balancing Act Between Danger Signaling and Pro-Survival.
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DOI:
10.1161/circresaha.116.306588
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发表时间:
2016-06-10
影响因子:
20.1
通讯作者:
Motterlini R
Motterlini R
中科院分区:
医学1区
文献类型:
--
作者:
Otterbein LE;Foresti R;Motterlini R

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了解心脏损伤后修复和再生能力的过程对于开发转化医学解决方案至关重要。新的探索途径包括心脏细胞治疗和靶向细胞死亡和再生的细胞重编程。一个有吸引力的可能性是利用细胞保护基因,存在的自我保护过程,并促进和支持细胞的生存。虽然抗氧化剂和热休克蛋白被包括在这一类中,但作为主要保护性前哨的一种酶受到了大量关注,这是血红素加氧酶-1(HO-1),其是血红素催化成生物活性信号分子一氧化碳、胆绿素和铁的限速步骤。归因于HO-1的显著的心脏保护作用通过其调节炎症过程、细胞信号传导和线粒体功能的能力得到最好的证明,最终减轻心肌组织损伤和血管增殖性疾病的进展。我们在这里讨论HO-1和血红素对心血管健康的作用的新见解,重要的是,它们如何被利用来促进损伤后的心脏修复。
Understanding the processes governing the ability of the heart to repair and regenerate after injury is crucial for developing translational medical solutions. New avenues of exploration include cardiac cell therapy and cellular reprogramming targeting cell death and regeneration. An attractive possibility is the exploitation of cytoprotective genes that exist solely for self-preservation processes and serve to promote and support cell survival. While the antioxidant and heat shock proteins are included in this category, one enzyme that has received a great deal of attention as a master protective sentinel is heme oxygenase-1 (HO-1), the rate-limiting step in the catabolism of heme into the bioactive signaling molecules carbon monoxide, biliverdin and iron. The remarkable cardioprotective effects ascribed to HO-1 are best evidenced by its ability to regulate inflammatory processes, cellular signaling and mitochondrial function ultimately mitigating myocardial tissue injury and the progression of vascular-proliferative disease. We discuss here new insights into the role of HO-1 and heme on cardiovascular health, and importantly, how they might be leveraged to promote heart repair after injury.