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oai:repisalud.isciii.es:20.500.12105/127322024-09-27T08:30:14Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607

00925njm 22002777a 4500 dc MacGrogan, Donal author Martinez-Poveda, Beatriz author Desvignes, Jean-Pierre author Fernandez-Friera, Leticia author Gomez, Manuel J author Gil Vilariño, Eduardo author Callejas Alejano, Sergio author Garcia-Pavia, Pablo author Solis, Jorge author Lucena, Joaquín author Salgado, David author Collod-Béroud, Gwenaelle author Faure, Emilie author Théron, Alexis author Torrents, Julia author Avierinos, Jean-François author Montes, Lorena author Dopazo, Ana author Fuster, Valentin author Ibáñez, Borja author Sanchez-Cabo, Fatima author Zaffran, Stephane author de la Pompa, Jose Luis author 2020-12-07 Calcific aortic valve disease (CAVD) is a significant cause of illness and death worldwide. Identification of early predictive markers could help optimize patient management. RNA-sequencing was carried out on human fetal aortic valves at gestational weeks 9, 13, and 22 and on a case-control study with adult noncalcified and calcified bicuspid and tricuspid aortic valves. In dimension reduction and clustering analyses, diseased valves tended to cluster with fetal valves at week 9 rather than normal adult valves, suggesting that part of the disease program might be due to reiterated developmental processes. The analysis of groups of coregulated genes revealed predominant immune-metabolic signatures, including innate and adaptive immune responses involving lymphocyte T-cell metabolic adaptation. Cytokine and chemokine signaling, cell migration, and proliferation were all increased in CAVD, whereas oxidative phosphorylation and protein translation were decreased. Discrete immune-metabolic gene signatures were present at fetal stages and increased in adult controls, suggesting that these processes intensify throughout life and heighten in disease. Cellular stress response and neurodegeneration gene signatures were aberrantly expressed in CAVD, pointing to a mechanistic link between chronic inflammation and biological aging. Comparison of the valve RNA-sequencing data set with a case-control study of whole blood transcriptomes from asymptomatic individuals with early aortic valve calcification identified a highly predictive gene signature of CAVD and of moderate aortic valve calcification in overtly healthy individuals. These data deepen and broaden our understanding of the molecular basis of CAVD and identify a peripheral blood gene signature for the early detection of aortic valve calcification. Physiol Genomics. 2020; 52(12):563-574 1094-8341 http://hdl.handle.net/20.500.12105/12732 33044885 10.1152/physiolgenomics.00034.2020 1531-2267 Physiological genomics CAVD gene signature human fetal valve inflammation peripheral blood biomarker Identification of a peripheral blood gene signature predicting aortic valve calcification.