Abstract P007: Overexpression Of Mitochondrial Transcription Factor A Attenuates Mitochondrial Damage And Hypertension-induced Aged Kidney Injury

Abstract

Aging-induced changes in the kidney are associated with reduction of mitochondria and increased mitochondrial abnormalities. The presence of hypertension in the aging population has additional deleterious effects that alters redox balance and impairs mitochondrial function. Mitochondrial transcription factor A (TFAM) is an important regulator of mitochondrial genes that play crucial roles in maintaining mitochondrial stability and replication. In the kidney, the expression of TFAM decreases with aging to promote sclerosis; however, its role in combination with hypertension has not been studied. The purpose of the study was to investigate whether overexpression of TFAM in the aging mice mitigates hypertension-induced kidney damage. We treated 68-70 wk old, male C57BL/6J (WT) and transgenic mice overexpressing TFAM (Tg, based on C57 background) with Angiotensin-II (1000 ng/kg/min) for 4-week period. Tg mice had lower blood pressure, increased mitochondrial copy number, decreased mitochondrial lipid peroxidation, and better renal function compared to WT groups. The changes were associated with decreased inflammation, reduced wnt signaling and pro-fibrotic markers. Taken together, our results suggest that overexpression of TFAM and reduction of wnt activation reduces hypertension induced renal injury in aged mice by modulating mitochondrial bioenergetics and maintaining homeostasis between inflammation and fibrosis.