Role of vitamin A in the formation of congenital heart defects.
Retinoic acid, the biologically active form of vitamin A, is a critical player in normal development. The concentration of retinoic acid is highly regulated by the embryo to prevent either a deficit or an excess of this molecule, conditions that have been shown to produce cardiac defects that vary depending on the severity and the timing of the insult. The vast majority of these defects are associated with the valves or the membranous septa of the heart, suggesting a problem with the formation of the cardiac mesenchyme from both within and outside the heart. While the exact role of retinoic acid in cardiac development is not known, it is believed that retinoic acid influences development by up- or down-regulating cardiac specific genes. This review briefly discusses the role of cardiac mesenchyme and cardiac neural crest in septation of the heart. This is followed by a discussion of vitamin A metabolism and the cardiac defects associated with abnormal levels of retinoic acid. Finally, a mechanism is proposed concerning the ways abnormal levels of retinoic acid lead to similar cardiac defects by disrupting the production of the extracellular matrix.
Sinning
A R
AR
Department of Anatomy, University of Mississippi Medical Center in Jackson, 39216-4505, USA. asinning@anatomy.umsmed.edu
D000818:Animals; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000196:embryology; D006330:Heart Defects, Congenital / Q000139:chemically induced / Q000378:metabolism*; D006801:Humans; D008648:Mesoderm / Q000378:metabolism; D009432:Neural Crest / Q000196:embryology; D012857:Situs Inversus; D014212:Tretinoin / Q000633:toxicity; D014801:Vitamin A / Q000378:metabolism*
D014801:Vitamin A; D014212:Tretinoin