A remarkable adaptive paradigm of heart performance and protection emerges in response to marked cardiac-specific overexpression of ADCY8.

Autor:	Tarasov KV; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Chakir K; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Riordon DR; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Lyashkov AE; Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, United States., Ahmet I; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Perino MG; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Silvester AJ; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Zhang J; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Wang M; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Lukyanenko YO; Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, United States., Qu JH; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Barrera MC; Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, United States., Juhaszova M; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Tarasova YS; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Ziman B; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Telljohann R; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Kumar V; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Ranek M; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States., Lammons J; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Bychkov R; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., de Cabo R; Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, United States., Jun S; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States., Keceli G; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States., Gupta A; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States., Yang D; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Aon MA; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Adamo L; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States., Morrell CH; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Otu W; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Carroll C; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Chambers S; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Paolocci N; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States., Huynh T; Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States., Pacak K; Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States., Weiss R; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, United States., Field L; Kraennert Institute of Cardiology, Indiana University School of Medicine, Idianapolis, United States., Sollott SJ; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States., Lakatta EG; Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2022 Dec 14; Vol. 11. Date of Electronic Publication: 2022 Dec 14.
DOI:	10.7554/eLife.80949
Abstrakt:	Adult (3 month) mice with cardiac-specific overexpression of adenylyl cyclase (AC) type VIII (TG AC8 ) adapt to an increased cAMP-induced cardiac workload (~30% increases in heart rate, ejection fraction and cardiac output) for up to a year without signs of heart failure or excessive mortality. Here, we show classical cardiac hypertrophy markers were absent in TG AC8 , and that total left ventricular (LV) mass was not increased: a reduced LV cavity volume in TG AC8 was encased by thicker LV walls harboring an increased number of small cardiac myocytes, and a network of small interstitial proliferative non-cardiac myocytes compared to wild type (WT) littermates; Protein synthesis, proteosome activity, and autophagy were enhanced in TG AC8 vs WT, and Nrf-2, Hsp90α, and ACC2 protein levels were increased. Despite increased energy demands in vivo LV ATP and phosphocreatine levels in TG AC8 did not differ from WT. Unbiased omics analyses identified more than 2,000 transcripts and proteins, comprising a broad array of biological processes across multiple cellular compartments, which differed by genotype; compared to WT, in TG AC8 there was a shift from fatty acid oxidation to aerobic glycolysis in the context of increased utilization of the pentose phosphate shunt and nucleotide synthesis. Thus, marked overexpression of AC8 engages complex, coordinate adaptation "circuity" that has evolved in mammalian cells to defend against stress that threatens health or life (elements of which have already been shown to be central to cardiac ischemic pre-conditioning and exercise endurance cardiac conditioning) that may be of biological significance to allow for proper healing in disease states such as infarction or failure of the heart. Competing Interests: KT, KC, DR, AL, IA, MP, AS, JZ, MW, YL, JQ, MB, MJ, YT, BZ, RT, VK, MR, JL, RB, Rd, SJ, GK, AG, DY, MA, LA, CM, WO, CC, SC, NP, TH, KP, RW, LF, SS, EL No competing interests declared
Databáze:	MEDLINE
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