Hyperglycemic cardiac growth project
Congenital heart disease (CHD) is the leading non-infectious cause of death among infants. The Hinds Lab is interested in the role of hyperglycemia on cardiac development. CHDs affect 1% of newborn infants, with maternal diabetes leading to a 3 to 5-fold increase in cardiac malformations. While genetic defects are known to cause cardiac malformations, elevated blood glucose has been shown to be responsible for many heart defects observed in humans and the mechanisms by which this takes place are not well understood.
Our goal is to implement a combination of engineering and biological tools to understand the mechanisms by which hyperglycemia affects cardiac development. In order to do this, we use a chick embryo model and induce a state of hyperglycemia during the period of early cardiac development. The chick embryo is an excellent model as the embryos are easy to access and transparent, allowing for observation without interrupting cardiac growth. The chick model is unique compared with other mammalian models as it allows for the control of the timing of the induction of hyperglycemia, the extent to which it is induced, and the embryo is not influenced by the mother, conveniently allowing us to identify any effects of embryonic hyperglycemia alone.
We utilize state of the art imaging techniques to visualize the response of cardiac tissue to hyperglycemic conditions. Our experiments are complemented by computational investigation of structural changes in the developing heart. We study the protein expression, blood flow velocities, histological composition, and structural differences of portions of the developing heart. Together, our data suggests that hyperglycemia acts as a major teratogen and impacts cardiac tissue growth and remodeling.
Hyperglycemia for 4 days of chicken embryo incubation caused a reduction in cell proliferation in cardiac tissue due to suppression of the cell cycle, specifically the upregulation of P21 and downregulation of cyclin D1. Published as: Figure 4 in Scott-Drechsel D, Rugonyi S, Marks D, Thornburg K, and Hinds M. (2013). Hyperglycemia Slows Embryonic Growth and Suppresses Cell Cycle via Cyclin D1 and p21. Diabetes (62):234-242.