Heme oxygenase/carbon monoxide system and development of the heart

Mahan, Vicki L.1,2,*

1Department of Surgery, Queen Elizabeth Central Hospital, Blantyre, Malawi2Drexel University Medical School, Phildelphia, PA, USA

Abstract

Progressive differentiation controlled by intercellular signaling between pharyngeal mesoderm, foregut endoderm, and neural crest-derived mesenchyme is required for normal embryonic and fetal development. Gasotransmitters (criteria: 1) a small gas molecule; 2) freely permeable across membranes; 3) endogenously and enzymatically produced and its production regulated; 4) well-defined and specific functions at physiologically relevant concentrations; 5) functions can be mimicked by exogenously applied counterpart; and 6) cellular effects may or may not be second messenger-mediated, but should have specific cellular and molecular targets) are integral to gametogenesis and subsequent embryogenesis, fetal development, and normal heart maturation. Important for in utero development, the heme oxygenase/carbon monoxide system is expressed during gametogenesis, by the placenta, during embryonic development, and by the fetus. Complex sequences of biochemical pathways result in the progressive maturation of the human heart in utero. The resulting myocardial architecture, consisting of working myocardium, coronary arteries and veins, epicardium, valves and cardiac skeleton, endocardial lining, and cardiac conduction system, determines function. Oxygen metabolism in normal and maldeveloping hearts, which develop under reduced and fluctuating oxygen concentrations, is poorly understood. “Normal” hypoxia is critical for heart formation, but “abnormal” hypoxia in utero affects cardiogenesis. The heme oxygenase/carbon monoxide system is important for in utero cardiac development, and other factors also result in alterations of the heme oxygenase/carbon monoxide system during in utero cardiac development. This review will address the role of the heme oxygenase/carbon monoxide system during cardiac development in embryo and fetal development.

摘要：正常胚胎发育需要咽中胚层、前肠内胚层和神经嵴源性间充质之间由细胞间信号控制的渐进分化。气体递质是一种小气体分子，可自由渗透穿越膜，由内源性和酶促作用产生及调节。气体递质可在生理浓度下发挥特定的功能，且其功能可被外源性分子模仿。气体递质的细胞效应可能是也可能不是由第二信使介导的，其具有特定的细胞和分子靶点。因此气体递质是配子发生和随后的胚胎发生、胎儿发育和正常心脏成熟的重要组成部分。血红素加氧酶/一氧化碳系统对宫内发育十分重要，在配子发生、胎盘、胚胎发育和胎儿中均有表达。复杂的生化步骤使得人心脏在子宫内逐渐成熟，并产生的心肌结构，包括心肌、冠状动静脉、心外膜、瓣膜和心脏骨骼、心内和心脏传导系统，进而产生对应的功能。目前对于在氧气浓度降低和波动的情况下，正常和发育不良的心脏的氧代谢情况知之甚少。但是“正常”缺氧对心脏形成至关重要，而子宫内“异常”缺氧则会影响心脏发生。血红素加氧酶/一氧化碳系统对子宫内心脏发育很重要，其他因素也会导致子宫内心脏发展过程中血红素加氧基/一氧化碳系统的变化。此次综述拟探索血红素加氧酶/一氧化碳系统在胚胎心脏发育过程中的作用。