Heme oxygenase/carbon monoxide system and development of the heart

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.