Comparative analysis of miRNA profile in sheep serum and serum-derived extracellular vesicles before and after single stage Fontan surgery

There are no curative treatment options for patients with single ventricle disease. Rather, the standard of care includes a series of palliative procedures that culminate in the Fontan operation, which, while life-saving, nevertheless reduces longevity and quality of life. The cause of late term death in these patients is typically ascribed to insidious end organ sequelae associated with the Fontan circulation. The etiology underlying these pathological processes remains unknown, but is thought to be diverse and multifactorial, arising from progressive deterioration of end-organ function due to the non-physiologic Fontan hemodynamics and its consequences on tissue perfusion and remodeling.Our overall goal is to evaluate the impact of Fontan physiology on cardiopulmonary remodeling over long periods in an ovine Fontan survival model. Adolescent sheep with otherwise normal biventricular cardiac anatomy underwent a single-stage Fontan. Examination of miRNA content in serum and serum-EV with and without Fontan surgery is included in this study. Our overall future experimental approach is to pair serial evaluation of the cardiovascular function by MRI, echo and catheterization with RNAseq, immuno-histology, and biomechanical assessments at prescribed endpoints to examine adverse remodeling in response to Fontan-induced hemodynamics.