title: Folate, homocysteine and the cardiac neural crest.
abstract: Congenital heart defects (CHD) are the most common congenital defects worldwide, and perigestational folate supplementation (PFS) is the most effective large-scale intervention to date for reducing CHD. This review is based upon the following premises: that the majority of CHD result from disruption of development of the cardiac neural crest (CNC); and that the CNC is highly responsive to folate and homocysteine. The following roles of folate are discussed in relation to CNC development: one-carbon metabolism in support of mitosis and gene methylation; and gene regulation via direct activity of the folate receptor. The following roles of hyperhomocysteinemia are discussed in the same context: increased oxidative stress; disruption of gene methylation; homocysteinylation of key proteins; and NMDA receptor binding. It is proposed that well-focused advances in folate-CNC research could lead to development of strategies, in addition to PFS, to facilitate normal CNC and heart development, and thereby further reduce CHD.
authors: Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA. throsenq@unmc.edu
authors: Thomas H
authors: TH
authors: Rosenquist
mesh_terms: D000818:Animals; D019175:DNA Methylation; D058975:Folate Receptor 1 / Q000378:metabolism; D005492:Folic Acid / Q000378:metabolism*; D006330:Heart Defects, Congenital / Q000196:embryology / Q000378:metabolism*; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D008938:Mitosis; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism*
chemical_list: D058975:Folate Receptor 1; D006710:Homocysteine; D005492:Folic Acid