Abstract P330: Alterations in Maternal Heart during Diabetic Rat Pregnancy

Abstract

Introduction: Pregnancy is an enormous challenge for the maternal cardiovascular system. Women with pre-gestational cardiovascular impairments face an increased risk for developing pathological pregnancies. Diabetes affects cardiovascular function already in the non-pregnant state. We aimed at evaluating the influence of pre-gestational diabetes on heart morphology and gene expression using a transgenic rat. Methods: We generated a pre-gestational hyperglycemic condition in transgenic rats (Tet29) by applying doxycycline, which induces a knock down of the insulin receptor via RNA interference in this strain. Wildtype Sprague-Dawley (SD) rats receiving doxycycline served as a control. Heart analysis was performed on day 21 of pregnancy (with appearance of a vaginal plug being pregnancy day 1). Gene expression levels were measured by qRT-PCR. Heart and body weight were obtained and analyzed. Results: Tet29 rats were hyperglycemic throughout pregnancy (blood glucose of 487±24 mg/dl vs. 95±5 md/dl in SD rats) and had a lower body weight in comparison to SD rats at the end of pregnancy (402.3±9.0 g vs. 471.3±12.0 g). Hearts of diabetic Tet29 rats were smaller (absolutely and relatively, regarding body weight), in comparison to SD rats at the end of pregnancy (0.60±0.02 g vs. 0.87±0.02 g; 0.150±0.005 vs. 0.186±0.004, respectively). Expression of inflammation markers MCP1 (1.34±0.20 vs. 0.47±0.13) and TNFα (1.76±0.30 vs. 0.48±0.15) was higher in diabetic hearts. Additionally, the expression of the fibrosis markers CTGF (1.83±0.98 vs. 0.18±0.04) and NGAL (1.30±0.55 vs. 0.41±0.22) was elevated in diabetic hearts, whereas the markers fibronectin (0.74±0.07 vs. 1.23±0.29) and collagen 1 (0.45±0.08 vs. 2.04±0.55) were decreased. Discussion: Diabetic pregnant Tet29 rats reveal an altered morphology and gene expression profile in the heart. This phenotype does not fit in a classical category of heart diseases. Further studies such as echocardiography and follow-up analysis in postpartum life are necessary to elucidate possible functional changes.