Abstract 1131: Delivery Of Allogeneic Mitochondria Reverses Signatures Of Endothelial Aging & Senescence

Abstract

Mitochondrial dysfunction is a key factor in vascular aging, including endothelial cell (EC) dysfunction. This research investigates whether introducing mitochondria from allogeneic fibroblasts into human microvascular ECs can mitigate the cellular abnormalities associated with aging. Mitochondria were transferred into ECs of different passages (p6-14) using centrifugation. Post mito-transfer, the metabolic activity, mitochondrial network (density), and the proliferative capacity of ECs were evaluated through extracellular flux analysis, confocal microscopy, and 5-ethynyl-2'-deoxyuridine incorporation (proliferation assay), respectively. Results show that compared to age matched control ECs, mito-transferred ECs exhibited no change in their oxygen consumption rates linked to mitochondrial respiration. Additionally, while early passage ECs (p6-7) had no change in glycolytic activity (compared to controls), middle (p10-11) and late passage ECs (p10-14) had considerable increases in their glycolytic activity post mito-transfer. Mitochondrial network analysis additionally revealed that the mitochondrial density of early passage ECs were unaffected by mito-transfer, while late passage ECs had enhanced mitochondrial networks, including total volume, and branching post mito-transfer. Lastly, late passage ECs demonstrated a 25% increase in proliferation after mito-transfer. These findings indicate that aging in ECs is linked to increased oxidative phosphorylation metabolism, and that mito-transfer can reduce senescence-associated oxidative glucose metabolism and enhance EC proliferation. This positions mito-transfer as a promising strategy for improve EC function in cardiovascular aging.