253 IMPACT OF LOW BIRTH WEIGHT ON THE EXPRESSION OF THE RENIN-ANGIOTENSIN SYSTEM, FACTORS WHICH REGULATE AUTOPHAGY, FIBROSIS AND CAPILLARY DENSITY IN THE HEART DURING EARLY POSTNATAL LIFE

Abstract

Background: Low birth weight (LBW) is associated with increased hypertension in offspring. RAS is important in hypertension but is also implicated in cardiac angiogenesis, remodelling and autophagy. We aimed to investigate the effects of LBW on the cardiac RAS and these cardiac processes. Methods: Plasma renin activity and ANGII in average birth weight (ABW) and LBW lambs at d20 were determined using radioimmunoassay. Left ventricle samples were collected from the lambs at d21 for the analysis of gene and protein expression. Results: There was increased plasma renin activity and ANGII concentrations in LBW compared to ABW lambs. There was increased ACE2 mRNA and decreased abundance of ATR1 but no changes in abundance of ACE or ATR2 in LBW compared to ABW lambs. There was increased phospho-Akt protein and decreased capillary density in the heart of LBW lambs compared to ABW lambs. There was decreased collagen I and II mRNA expression but no evidence of cardiac remodelling or fibrosis in the LBW lambs. There was decreased FoxO1 and FoxO3a protein in the LBW lambs compared to ABW lambs, but no changes in autophagy proteins: phospho-FoxO1, phospho-FoxO3a, Beclin1, LC3B and LAMP1 was not altered in LBW lambs. Conclusion: Although circulating and local cardiac RAS components were altered in LBW lambs there was no increase in fibrosis or autophagy in the heart of the LBW lamb. LBW resulted in decreased capillary density during early postnatal life and this may result in an increased risk of impaired heart function in later life.