Example：10.1021/acsami.1c06204 or Chem. Rev., 2007, 107, 2411-2502
Identification of a peripheral blood gene signature predicting aortic valve calcification Physiological Genomics (IF3.107), Pub Date : 2020-10-12, DOI: 10.1152/physiolgenomics.00034.2020 Donal MacGrogan, Beatriz Martínez-Poveda, Jean-Pierre Desvignes, Leticia Fernandez-Friera, Manuel José Gomez, Eduardo Gil Vilariño, Sergio Callejas Alejano, Pablo García-Pavía, Jorge Solis, Joaquín Lucena, David Salgado, Gwenaelle Collod-Béroud, Emilie Faure, Alexis Théron, Julia Torrents, Jean-François Avierinos, Lorena Montes, Ana Dopazo, Valentín Fuster, Borja Ibáñez, Fátima Sánchez-Cabo, Stephane Zaffran, José Luis de la Pompa
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 non-calcified 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 re-iterated developmental processes. The analysis of groups of co-regulated 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 ageing. Comparison of the valve RNA-sequencing dataset 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.