200: Parity is not associated with increased atherosclerosis in a mouse model

Abstract

atherosclerosis in a mouse model Hai-Lang Duong, Kristine Lain, Deborah Howatt, Debra Rateri, Alan Daugherty, Thomas Curry University of Kentucky, Obstetrics and Gynecology, Lexington, KY, Norton Healthcare, Maternal-Fetal Medicine, Louisville, KY, University of Kentucky, Saha Cardiovascular Research Center, Lexington, KY OBJECTIVE: The correlation of parity to cardiovascular (CV) risk later in life has not been clearly elucidated. Using a genetically modified strain of mice susceptible to atherosclerosis, we hypothesized that there is increased atherogenesis in parous mice compared to nulliparous mice. STUDY DESIGN: A total of 38 age-matched, female, low density lipoprotein receptor (LDLr)-/mice were initially fed normal laboratory diet. At 2 months of age, 19 mice were impregnated and delivered pups three consecutive times. The other 19 mice were never bred. At 8 months of age, all mice were fed a fat-enriched diet, which promotes hypercholesterolemia. After 11 weeks on this diet, the mice were euthanized. The intimal surface of the aorta was exposed and the total area of intima from the aortic arch through the thorax was measured. Quantification of atherosclerotic lesions on the intimal surface was performed using en face analysis. For this analysis, atherosclerotic lesions were measured in the arch and thoracic regions; lesion area (LA) was then calculated as a percentage of the total intimal surface area. Non-fasting, serum total cholesterol (TC) levels were also measured. Statistical analyses used either the Wilcoxon rank sum test or the Student’s t-test. RESULTS: LA in the combined arch and thorax regions of the parous mice (median 19.5%) did not differ from that of the nulliparous mice (median 18.8%, p 0.49, Table 1). In the parous mice, LA within the arch region was 34.9%, compared to 33.8% (p 0.60) in the nulliparous mice. Within the region of the thorax, LA measured 0.74% in the parous mice, compared to 0.79% (p 0.50) in the control mice. The two groups of mice did not differ in weight (p 0.14) or serum TC (p 0.75). CONCLUSION: Using a well-established mouse model for atherogenesis, we observed no difference in aortic atherosclerosis in parous mice compared to nulliparous mice. Our results suggest that, in this model, there is no effect of pregnancy on the development of atherosclerosis. Higher parity or exposure to an atherogenic diet during pregnancy may be necessary to reveal a link between parity and CV disease. 201 Beta oxidation of fatty acids in term human placentas Hector Mendez-Figueroa, Edward Chien, Nicole L. Nesbitt, Sivakama S. Bharathi, Eric Goetzman Women & Infants Hospital of RI and the Warren Alpert Medical School of Brown University, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Providence, RI, Childrens Hospital of Pittsburgh, Department of Pediatrics, Pittsburgh, PA OBJECTIVE: Fatty acid (FA) metabolism in human placentas has not been well illustrated. Distribution across gestation as well as the enzyme activity level has not been elucidated. We propose to determine normal expression and function of enzymes involved in FA metabolism in term human placentas as well as the impact labor has on the pathway STUDY DESIGN: Samples were collected within 10 minutes of delivery from patients presenting for: a) scheduled non-labored cesarean section and b) normal vaginal delivery 37 weeks. 1) Expression: Enzyme detection was done via western blot against: 5 Acyl-CoA dehydrogenase (ACAD) enzymes VLCAD, LCAD, MCAD, SCAD, ACAD9; Long and short-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD, SCHAD), Long chain 3-Ketoacyl CoA thiolase (LKAT) and complex II and V of the electron transport chain (ETC). 2) Function: A) Overall pathway function was tested using 3H palmitic and 3H octanoic acid via an explant placental tissue protocol. B) ACAD activities: VLCAD, LCAD, MCAD and SCAD function was measured with the anaerobic electron transfer flavoprotein (ETF) fluorescence reduction assay. C) Activity of the ETC complex I was assessed the commercially available Complex I “dipstick assay” D) ATP concentration was measured using a colorimetric kit RESULTS: Oxidation rates for C16 and C8 were roughly 20X less than that seen in fed-state mouse liver (C16 49.3 / 4.3, C8 435 / 50 pmoles/mg/hr). C16 metabolism in non-laboring placentas was significantly increased compared to labor. ATP concentration was significantly decreased with labor (0.61 vs. 0.41, p 0.027). Key FA oxidation enzymes are not only expressed in placenta but also maintain their enzymatic activities (Figure 1, Table 1) CONCLUSION: Term human placentas metabolize FA at a rate approximately 20X less than liver. C16 metabolism is reduced with the onset of labor, probably secondary to a decrease in available ATP. MCAD and SCAD enzymatic activity is not absent (or nearly absent) in human placentas as previously suggested. The presence of all five ACAD enzymes indicate that the FAO pathway plays an important role in placentas. www.AJOG.org Clinical Obstetrics, Medical-Surgical-Disease, Neonatology, Physiology-Endocrinology Poster Session I