Physiologic Cardiac Hypertrophy During Pregnancy Involves A Change In Gene Expression Regulating Cardiac Metabolism

Pregnancy is a chronic volume-overload state that necessitates maternal cardiovascular adaptations in order to support fetal development. Conscious dogs were studied using echocardiography before (Control), 60 days (60D) of pregnancy, and ~14 days post partum (PP). The Left Ventricular (LV) end-diastolic diameter, LV end-diastolic volume, heart rate, stroke volume, and cardiac output were significantly elevated at 60D vs. control (9%, 11%, 27%, 12% and 40% respectively, all p<0.05), and returned to normal levels PP. LV free wall mass was significantly larger in hearts at 60D (21% increase, p<0.05), indicating ventricular hypertrophy. We examined the changes in gene expression at those time points via the Affymetrix GeneChip® Canine Genome Array. We found elevated mRNA levels of genes that were indicative of cardiac hypertrophy, i.e.: MHC class II DLA beta chain; Microtubule-associated protein 1B; cardiac ankyrin repeat protein, metalloproteinase 9; myomegalin (80%, 61%, 60%, 52%, and 50% respectively, all p<0.05). Genes responsible for myocyte calcium signaling; sarcoplasmic reticulum Ca2+-transport ATPase; and cardiac ryanodine receptor 2 were significantly elevated (100%, and 60% respectively, p<0.05). Genes associated with glucose and glycogen metabolism such as; glycogen phosphorylase; pyruvate dehydrogenase; 6-phosphofructokinase were down regulated (−1.7, −1.6, −1.6 Fold change respectively, all p<0.05). Genes involved in free fatty acid oxidation such as isocitrate dehydrogenase; 3-ketoacyl-CoA thiolase; acetyl-coenzyme A synthetase (1.6, 1.6, 1.5 Fold change respectively, all p<0.05) among others were elevated. This indicates that during normal pregnancy the heart adapts by hypertrophy, increasing calcium signaling (inotropic state) and emphasizing FFA metabolism over glucose metabolism.