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American Heart Association

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Final ID: 4117594

Fetal Synthetic Glucocorticoid (sGC) Exposure Results in Later Life Cardiac Dysfunction and Ventricular Remodeling in Male Baboon Offspring

Abstract Body (Do not enter title and authors here): The “theory of developmental origins of health and disease” posits that stress in critical developmental periods will program life-course health and may affect cardiovascular (CV) health. Mothers at risk for premature delivery receive synthetic glucocorticoids (sGC) to enhance fetal lung maturation and manage fetal respiratory distress, but sGC exposure is linked to long-term CV dysfunction in offspring. Four groups of male baboons were studied: sGC exposed in utero at middle age (sGC-MA, 13.8±0.2Y), older sGC exposed in utero (sGC-O, 17.1±0.4Y), middle age unexposed (CTR-MA, 13.5±0.6Y), and older, unexposed baboons (CTR-O, 17.4±0.4Y). Gated, breath-hold, cine cardiac magnetic resonance imaging was performed at 3 Tesla (Siemens TIM Trio) to assess left ventricular (LV) function and myocardial strain, analyzed using cvi42® software. Mitochondrial electron transport chain (ETC) complex activity was analyzed using LV tissue from sGC-O and CTR-O euthanized baboons. Protein quantification was used to measure mitochondrial function and RNA-seq assessed differential gene expression and gene ontology (GO) enrichment. Unpaired t-tests were used. Data are reported as mean ± SD. Stroke volume and ejection fraction were similar in the elderly groups (4 sGC-O, 8 CTR-O). However, higher end-systolic and end-diastolic sphericity indexes (SI) and shorter LV axis lengths indicated remodeling. Also, global longitudinal and radial strains were reduced (both p<0.04) in sGC-O vs. CTR-O. Reduced LV cardiac output (p=0.005) was found in 5 sGC-MA animals vs 4 sGC-O animals, but not in 5 CTR-MA vs 8 CTR-O. In sGC-MA vs sGC-O, but not CTR-MA vs CTR-O, significant increases in SI (p=0.001), radial strain (p=0.02), and longitudinal (p=0.03) strain were found, but LV axis length (p=0.03) was reduced. LV mitochondrial analysis in 4 sGC-O vs 4 CTR-O myocardial samples revealed 33.5% less ETC activity (p=0.002) and 19.8% less complex I expression (p=0.048) in sGC. LV RNA-seq identified 63 upregulated and 20 downregulated genes in the sGC-O samples. GO pathway enrichment included changes in heart contraction, wounding responses, and leukocyte regulation pathways. These findings indicate that fetal sGC exposure developmentally programs offspring with LV remodeling and long-term cardiac and gene expression changes in male baboons, the closest available experimental nonhuman primate species to man. Future studies on females will probe sexual dimorphism in developmental programming.
  • Yang, Bowen  ( University of Texas Health Science Center at San Antonio , San Antonio , Texas , United States )
  • Adekunbi, Daniel  ( University of Texas Health Science Center at San Antonio , San Antonio , Texas , United States )
  • Zhang, Chen  ( University of Texas Health Science Center at San Antonio , San Antonio , Texas , United States )
  • Huber, Hillary  ( Texas Biomedical Research Institute , San Antonio , Texas , United States )
  • Zhao, Feiyang  ( University of Texas Health Science Center at San Antonio , San Antonio , Texas , United States )
  • Camones, Raechel  ( University of Texas Health Science Center at San Antonio , San Antonio , Texas , United States )
  • Li, Jinqi  ( University of Texas Health Science Center at San Antonio , San Antonio , Texas , United States )
  • Moody, Alexander  ( University of Texas Health Science Center at San Antonio , San Antonio , Texas , United States )
  • Li, Cun  ( Texas Biomedical Research Institute , San Antonio , Texas , United States )
  • Cox, Laura  ( Wake Forest University School of Medicine , Winston-Salem , South Carolina , United States )
  • Wang, Lu  ( University of Texas Health Science Center at San Antonio , San Antonio , Texas , United States )
  • Salmon, Adam  ( University of Texas Health Science Center at San Antonio , San Antonio , Texas , United States )
  • Clarke, Geoffrey  ( University of Texas Health Science Center at San Antonio , San Antonio , Texas , United States )
  • Nathanielsz, Peter  ( University of Wyoming , Laramie , Wyoming , United States )
  • Author Disclosures:
    Bowen Yang: DO NOT have relevant financial relationships | Laura Cox: No Answer | Lu Wang: No Answer | Adam Salmon: No Answer | Geoffrey Clarke: DO NOT have relevant financial relationships | Peter Nathanielsz: DO NOT have relevant financial relationships | Daniel Adekunbi: No Answer | Chen Zhang: No Answer | Hillary Huber: DO NOT have relevant financial relationships | Feiyang zhao: DO NOT have relevant financial relationships | Raechel Camones: No Answer | Jinqi Li: No Answer | Alexander Moody: No Answer | Cun Li: No Answer
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Hypertrophic Cardiomyopathy: Making Hearts Stronger but Not Pathologic

Sunday, 11/17/2024 , 08:00AM - 09:15AM

Abstract Oral Session

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Sex-Specific Cardiac Remodeling, Mitochondrial Dysfunction, and Transcriptomic Changes in Elderly Baboon Offspring Following Prenatal Synthetic Glucocorticoid Exposure

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