Abstract 16422: Lower Mitochondrial-derived Peptide Humanin in Young Adults Born Preterm Vs. Term and Association with Left Ventricular Ejection Fraction

Introduction: Preterm (PT) birth is associated with increased risk of cardiovascular diseases (CVD) and heart failure. We previously reported left ventricular (LV) mitochondrial dysfunction in a rat model mimicking the deleterious conditions associated with PT birth. Whether mitochondrial function is altered in humans born PT and associated with LV function changes is unknown. We aimed to determine if serum humanin levels, a mitochondrial-derived peptide with cytoprotective effects, are altered in humans born PT and are associated with impaired myocardial function. Methods: Data were obtained from 55 young adults born PT (<30 weeks of gestational age, GA) compared to 54 full-term (T) controls of the same age. Serum humanin levels were determined by ELISA and LV ejection fraction (LVEF) by echocardiography. Results are shown as median (interquartile range) and comparisons between groups were performed using non-parametric tests. Results: Individuals were evaluated at 23.3 (21.4, 25.3) years, and age and sex distribution were similar between groups. Median GA was 27.5 (26.2, 28.4) weeks in the PT group. Humanin levels (pg/ml) were 132.9 (105.1, 189.3) and 161.1 (123.6, 252) in the PT and the T groups, respectively (p=0.0414). LVEF was within the normal range and similar between groups. Lower LVEF was associated with lower humanin levels (p<0.001), and this association was observed both in the term (p=0.002) and the preterm (p=0.047) groups. Conclusions: Serum humanin levels are lower in adult born PT. Since lower humanin levels are also associated with lower LVEF, our results suggest that mitochondrial alterations could play a role in the long-term adverse cardiovascular consequences of PT birth. Humanin analogs improve LV function in experimental models. Our results pave the way for future studies exploring humanin as a therapeutic avenue for the prevention and treatment of CVD in individuals born PT.