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Physiologic Cardiac Hypertrophy During Pregnancy Involves a Change in Gene Expression Regulating Cardiac Metabolism
Author(s) -
Williams Jeffrey G,
Ojaimi Caroline,
Hintze Thomas H
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1188-b
Subject(s) - medicine , endocrinology , muscle hypertrophy , biology
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.