Retinoids and cardiovascular developmental defects

Vitamin A and related retinoids are critical regulators of normal cardiovascular development. Extreme variations in retinoid levels, too little or too much, dramatically alter embryonic morphogenesis that has teratogenic consequences, including effects on the heart and great vessels. Specific cardiovascular targets of retinoid action include effects on the anteroposterior patterning of the early heart, left-right decisions and cardiac situs, endocardial cushion formation, and, in particular, the neural crest. The cardiovascular defects produced are remarkably similar in deficiency and excess, suggesting modulation of common developmental or cellular processes by different levels of retinoids. The isolation of nuclear receptors that mediate retinoid action has led to the identification of some genes directly involved in the regulation of these processes and other gene products that may be affected more indirectly. This review will examine the mechanism of retinoid action, the requirements for vitamin A during normal heart development, and the consequences of nonphysiologic or teratogenic exposure.