Pregnancy-related deaths associated with cardiac events (preeclampsia, cardiovascular disease) have recently increased in the U.S. with a higher occurrence among African American and Hispanic women. Many signaling pathways have been associated with the physiological hypertrophy of the heart that occurs during pregnancy. However, how the pathways that control remodeling are activated and influenced during pregnancy has yet to be fully understood. There are metabolic adaptations that occur in the heart during pregnancy which may be being mediated and influenced by the intake of essential nutrients in the diet. Vitamin A is needed for the function of many organs and has been linked to the function of the adult heart. Retinoic acid is the active form of vitamin A that has been implicated in cardiac remodeling. However, whether or not retinoid are essential during the cardiac remodeling that occurs during pregnancy is still unknown. ?-carotene, primarily obtained from fruits and vegetables, is the most abundant dietary precursor of vitamin A and its derivatives (retinoids). ?-carotene can be cleaved asymmetrically by the mitochondrial ?-carotene 9?,10?-oxygenase (BCO2) to generate ?-apo- 10?carotenal, which can serve as a precursor of retinoids, but may also antagonize retinoic acid action. Our preliminary findings indicate that retinoic acid synthesis may be favored in the heart of wild-type (WT) mice during pregnancy, suggesting a potential role of the active vitamin A metabolite in sustaining maternal cardiac hypertrophy (remodeling). We found that Bco2 mRNA levels increased in the hypertrophic heart of WT dams at mid-gestation. In addition, in the absence of BCO2 (Bco2-/- mice) the maternal heart fails to enlarge during pregnancy. Based on these premises, we hypothesized that BCO2 may contribute to physiological hypertrophy of the maternal heart via the generations of ?-apo-10?-carotenal, which in turn could generate retinoic acid or antagonize its action. We propose two Specific Aims:
Aim 1 : To define the changes in BCO2 expression, retinoid and lipid metabolism in the maternal heart during pregnancy;
and Aim 2 : To test whether ?-apo-10?carotenal is essential for maternal cardiac hypertrophy. Understanding the role of carotenoid and retinoid metabolism in this process will allows us to ultimately design dietary preventative measures to potentially decrease adverse cardiac function during pregnancy.
During pregnancy the mother?s heart becomes physiologically enlarged. The molecular mechanisms underlying this process are not fully understood, yet are key to the health of the mother. Gaining a better understanding of the pathways mediating this hypertrophy will lead to improvement of the maternal cardiac health during pregnancy, reducing pregnancy-related deaths associated with cardiovascular diseases and cardiomyopathies.
