2026-04-29T07:23:37Zhttps://repisalud.isciii.es/rest/oai/request
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
Repisalud author 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 funder Ministerio de Ciencia, Innovación y Universidades (España) 2021-04-22T06:17:34Z 2021-04-22T06:17:34Z 2020-12-07 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 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. eng CAVD gene signature human fetal valve inflammation peripheral blood biomarker Identification of a peripheral blood gene signature predicting aortic valve calcification. journal article 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 URL https://repisalud.isciii.es/bitstreams/593956d9-a78f-46ad-8ae0-449d48b2483b/download File MD5 11549c7f20d8597dd1e760eeecddc185 8490968 application/pdf IdentificationOfaPeripheral_2020.pdf URL https://repisalud.isciii.es/bitstreams/2c27332b-334d-438a-8abf-e1315cb130ae/download File MD5 8e49bcdbedc4ee7b59144dac6dc6fb2e 44662724 application/pdf IdentificationOfaPeripheral_2020supp1.pdf URL https://repisalud.isciii.es/bitstreams/d78e8d3d-fb3e-4d9c-bdc4-7d9d44ba0ccd/download File MD5 d72746298beb1900ba530c699887dd07 87796 application/pdf IdentificationOfaPeripheral_2020supp2.pdf URL https://repisalud.isciii.es/bitstreams/412fb708-58fe-41f3-bf0d-cc034c4d0635/download File MD5 ce6b14ff197aa0de2b1b298e5468fe9a 2908067 application/octet-stream IdentificationOfaPeripheral_2020supp.zip URL https://repisalud.isciii.es/bitstreams/051f9526-0c3a-4458-a62b-8311d4dfa2c6/download File MD5 7908d4ff4bdd0a20261a6b9117cdce0f 76190 text/plain IdentificationOfaPeripheral_2020.pdf.txt URL https://repisalud.isciii.es/bitstreams/30ab7a7b-e160-41f5-aea9-a9ba616c5c74/download File MD5 429010a7d51d5e986e7cda054aae362d 10863 text/plain IdentificationOfaPeripheral_2020supp1.pdf.txt URL https://repisalud.isciii.es/bitstreams/f21205af-ebed-45e7-9deb-acaf3ab85352/download File MD5 effc475f90769d9ed19ae63a1834c131 3317 text/plain IdentificationOfaPeripheral_2020supp2.pdf.txt