Alberta Innovates Health Solutions (AIHS) 025 STRAIN-DEPENDENT DEFECT IN RIGHT VENTRICULAR ADAPTATION IN FISCHER RATS WITH SEVERE PULMONARY ARTERIAL HYPERTENSION IS ASSOCIATED WITH DYSREGULATION IN METABOLIC AND ANGIOGENIC PATHWAYS CM Seun, KR Chaudhary, Y Deng, B Jiang, DJ Stewart Ottawa, Ontario BACKGROUND: Fischer rats exhibit a very high mortality in the SU5416 (SU) / chronic hypoxia (CH) model of severe pul- monary arterial hypertension (PAH) compared to Sprague Dawley (SD) rats, despite nearly identical increases in right ventricular systolic pressure (RVSP). This was associated with greater dilatation and reduced function of the right ventricle (RV) suggesting a strain-specific defect in RV adaptation to increased afterload. The aim of this study was to explore the mechanisms responsible for this marked difference in compensatory remodeling of the RV that drives poor prog- nosis and high mortality. METHODS/RESULTS: PAH was induced by a single subcu- taneous injection SU (20mg/kg), or vehicle (Control) in 6- week SD (Harlan, USA) or Fischer rats (CDF, Charles River), followed by a 3-week exposure to CH (10% oxygen). Echo- cardiography (Vevo 2100, Visual Sonics) was performed weekly to assess RV structure and function, and revealed far greater RV dilatation (diastolic RV internal diameter/LV in- ternal diameter; RVID/LVID) and reduction in cardiac output in Fischer rats compared to SD. There was marked similar, elevation in RVSP and RV hypertrophy (RV/LV+S mass ratio) in SD and CDF rats in response to SU/CH; however, capillary density was significantly reduced in CDF rats as assessed by CD31 immunostaining and fluorescent microangiography. RNA expression was assayed in the RV at 4 weeks post SU using Affymetrix Rat Gene 2.0ST and Affymetrix miRNA 4.0 gene chips, showing a downregulation of genes related to fatty acid metabolism genes (SLC27A1, ACADSB, ACSL1, DECR1, LIPE, HADHA, CYP4B1), as well as peroxisome proliferator-activated Receptor gamma coactivator 1 a (PGC1a), which has previously been impli- cated in metabolic dysfunction of RV decompensation. A focused angiogenesis RT-PCR array showed significant blunting in the expression of a variety of genes related to angiogenesis and vascular homeostasis, including prosta- glandin synthase 1, endoglin and integrin beta chain beta 3, in CDF versus SD rats. CONCLUSION: Inadequate RV adaptation in response to severe PAH in CDF compared to SD rats is associated with blunted expression of genes critical in controlling myocardial meta- bolism and vascular growth, suggesting that strain-dependent defects in the regulation of these critical pathways underlies RV decompensation. Trainee Research Award Finalist - Basic Science 026 GESTATIONAL DIABETES PROGRAMS MITOCHONDRIAL DYSFUNCTION AND IMPAIRS CARDIAC FUNCTION IN THE OFFSPRING SM Kereliuk, KG Cheung, B Xiang, LK Cole, TJ Pereira, MA Fonseca, GM Hatch, J McGavock, VW Dolinsky Winnipeg, Manitoba BACKGROUND: Gestational diabetes mellitus (GDM) is the most common complication of pregnancy. Children of mothers that had GDM are at an increased risk for the development of cardiovascular and metabolic diseases later in life, though the mechanisms responsible for this observation are unknown. Mitochondria are the organelles responsible for cellular energy production and impaired function is associated with the development of cardiovascular disease. We propose that impaired mitochondrial function, programmed in utero, may be a contributing mechanism to cardiometabolic disease development and hypothesize that the hearts from offspring exposed to GDM will exhibit impaired mitochondrial bio- energetics and heart disease. METHODS: To induce GDM female rats were fed a high fat (45% kcal) and sucrose (HFS) diet prior to mating, throughout pregnancy and lactation. Lean control females received a low fat (LF; 10% kcal) diet. Ventricular myocytes were isolated from the hearts of fetal rat offspring (embryonic day 20) and mitochondrial respiration was analyzed using a Seahorse Biosciences Extracellular Flux Analyzer. To assess the interaction between prenatal GDM exposure and the influ- ence of the postnatal diet over the entire life course of the offspring, offspring were randomly assigned to HFS or LF diets after weaning. Serial echocardiography of the offspring S82 Canadian Journal of Cardiology Volume 32 2016