Vitamin A is supposed to be really good for you – improving your vision, complexion and even pre-natal health. But what does it do, exactly?
“That’s actually not very well known,” says Dr. Gregg Duester, professor in Sanford-Burnham’s Development and Aging program. “For example, even though it’s been clear for 100 years that vitamin A is required for proper embryonic development, only now are we getting to the molecular details of what it does.”
Researchers in Dr. Duester’s lab study retinoic acid, an active form of vitamin A. They are especially interested in understanding how retinoic acid tells the right body parts to form in the right places at the right time in a developing embryo. Recently, while comparing limb buds (the precursors of arms and legs) in mice with – and without – the ability to generate retinoic acid from vitamin A, they decided to check out the differences in their hearts, too. As it turns out, the ventricles (the part of the heart that pumps blood out to the rest of the body) in retinoic acid-deficient mouse embryos, were thinner than those in their normal counterparts.
To find out how retinoic acid impacts heart development, we first have to look at another organ altogether – the liver. In a study published in the January 2011 issue of the journal Development, Dr. Duester and his colleagues show that retinoic acid boosts production of erythropoietin in the liver at a certain stage in development. You may have heard of erythropoietin – some athletes abuse it as a performance-enhancing drug known as EPO. The reason EPO works is because erythropoietin boosts red blood cell production and red blood cells deliver oxygen to tired muscles. During development, the liver produces erythropoietin to increase red blood cell production as the growing embryo needs more and more oxygen.
So retinoic acid stimulates erythropoietin in the liver, but what does that have to do with heart development? What this paper also showed is that, when triggered by retinoic acid in the liver, erythropoietin travels to the heart, where it switches on a growth factor.
“What we are seeing is cross-talk between two developing organs – something that wasn’t really known to occur,” explains Dr. Thomas Brade, post-doctoral researcher in Dr. Duester’s lab and first author on the Development paper.
This newly identified molecular chain reaction (retinoic acid –> erythropoietin in liver –> growth factor in heart) causes heart ventricles to thicken at a particular point in embryonic development. If you think about it, this makes a lot of sense – early in development, an embryo is small and only needs to transport blood throughout a small area. But as the embryo grows and produces more blood, its heart needs the strength to pump it across greater distances.
In addition to answering some long-sought questions about embryonic development and the role of vitamin A (or retinoic acid), these findings also indicate that scientists might be able to exploit this growth factor to artificially expand heart tissue in the laboratory – or maybe even one day in patients with heart disease.
Brade T, Kumar S, Cunningham TJ, Chatzi C, Zhao X, Cavallero S, Li P, Sucov HM, Ruiz-Lozano P, & Duester G (2011). Retinoic acid stimulates myocardial expansion by induction of hepatic erythropoietin which activates epicardial Igf2. Development (Cambridge, England), 138 (1), 139-48 PMID: 21138976