Cardiac remodeling in a baboon model of intrauterine growth restriction mimics accelerated aging

Abstract

Extensive rodent studies have shown that reduced perinatal nutrition programs chronic cardiovascular disease. To enable translation to humans, we developed baboon offspring cohorts from mothers fed ad lib (control) or 70% ad lib diet in pregnancy and lactation, which were growth restricted (IUGR) at birth. We hypothesized that IUGR offspring hearts show impaired function and premature aging phenotype. We studied IUGR baboons (8 male, 8 female, 5.7 years), control offspring (8 male, 8 female, 5.6 years - human equivalent approximately 25 years), and normal elderly (OLD) baboons (6 male, 6 female, mean 15.9 years). Left ventricular (LV) morphology and systolic and diastolic function were evaluated with cardiac MRI and normalized to body surface area. Two-way ANOVA by group and sex (with p < 0.05) indicated ejection fraction, 3D sphericity indices, cardiac index, normalized systolic volume, normalized LV wall thickness, and average filling rate differed by group. Group and sex differences were found for normalized LV wall thickening and normalized myocardial mass, without interactions. Normalized peak LV filling rate and diastolic sphericity index were not correlated in CTL but strongly correlated in OLD and IUGR baboons. IUGR programming in baboons produces myocardial remodeling, reduces systolic and diastolic function, and results in the emergence of a premature aging phenotype in the heart. To our knowledge, this is the first demonstration of the specific characteristics of cardiac programming and early life functional decline with aging in an IUGR nonhuman primate model. Further studies across the life span will determine progression of cardiac dysfunction.

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