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Administration of Enalapril Started Late in Life Attenuates Hypertrophy and Oxidative Stress Burden, Increases Mitochondrial Mass, and Modulates Mitochondrial Quality Control Signaling in the Rat Heart

1
Fondazione Policlinico Universitario “Agostino Gemelli” IRCSS, Università Cattolica del Sacro Cuore, L.go A. Gemelli 1, 00168 Rome, Italy
2
Institute of Internal Medicine and Geriatrics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
3
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy
4
Institute of Surgical Sciences, Fondazione Policlinico Universitario “Agostino Gemelli” IRCSS, 00168 Rome, Italy
5
Department of Aging and Geriatric Research, Institute on Aging, Division of Biology of Aging, University of Florida, Gainesville, FL 32611, USA
6
Department of Medicine, Division of Gerontology, Geriatrics and Palliative Care, Nathan Shock Center of Excellence in the Basic Biology of Aging, University of Alabama at Birmingham, Birmingham, AL 35205, USA
*
Author to whom correspondence should be addressed.
These two authors contributed equally to this work.
Biomolecules 2018, 8(4), 177; https://doi.org/10.3390/biom8040177
Received: 11 September 2018 / Revised: 3 December 2018 / Accepted: 12 December 2018 / Published: 17 December 2018
(This article belongs to the Special Issue Mitochondrial Diseases)
Mitochondrial dysfunction is a relevant mechanism in cardiac aging. Here, we investigated the effects of late-life enalapril administration at a non-antihypertensive dose on mitochondrial genomic stability, oxidative damage, and mitochondrial quality control (MQC) signaling in the hearts of aged rats. The protein expression of selected mediators (i.e., mitochondrial antioxidant enzymes, energy metabolism, mitochondrial biogenesis, dynamics, and autophagy) was measured in old rats randomly assigned to receive enalapril (n = 8) or placebo (n = 8) from 24 to 27 months of age. We also assessed mitochondrial DNA (mtDNA) content, citrate synthase activity, oxidative lesions to protein and mtDNA (i.e., carbonyls and the abundance of mtDNA4834 deletion), and the mitochondrial transcription factor A (TFAM) binding to specific mtDNA regions. Enalapril attenuated cardiac hypertrophy and oxidative stress-derived damage (mtDNA oxidation, mtDNA4834 deletion, and protein carbonylation), while increasing mitochondrial antioxidant defenses. The binding of mitochondrial transcription factor A to mtDNA regions involved in replication and deletion generation was enhanced following enalapril administration. Increased mitochondrial mass as well as mitochondriogenesis and autophagy signaling were found in enalapril-treated rats. Late-life enalapril administration mitigates age-dependent cardiac hypertrophy and oxidative damage, while increasing mitochondrial mass and modulating MQC signaling. Further analyses are needed to conclusively establish whether enalapril may offer cardioprotection during aging. View Full-Text
Keywords: mitochondrial quality control; mitochondrial biogenesis; mitochondrial dynamics; mitophagy; mtDNA; TFAM binding; oxidative lesions; mtDNA damage; cardioprotection; peroxiredoxin mitochondrial quality control; mitochondrial biogenesis; mitochondrial dynamics; mitophagy; mtDNA; TFAM binding; oxidative lesions; mtDNA damage; cardioprotection; peroxiredoxin
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Picca, A.; Sirago, G.; Pesce, V.; Lezza, A.M.S.; Calvani, R.; Bossola, M.; Villani, E.R.; Landi, F.; Leeuwenburgh, C.; Bernabei, R.; Carter, C.S.; Marzetti, E. Administration of Enalapril Started Late in Life Attenuates Hypertrophy and Oxidative Stress Burden, Increases Mitochondrial Mass, and Modulates Mitochondrial Quality Control Signaling in the Rat Heart. Biomolecules 2018, 8, 177.

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