biostudies-literatureZhang RMNatural Sciences and Engineering Research Council of CanadaChina Scholarship CouncilMarfan FoundationCanadian Institutes of Health ResearchCIHR314https://www.ebi.ac.uk/biostudies/studies/S-EPMC11072253biostudies-literatureUnknown79(6)Thoracic aortic aneurysms (TAA) in Marfan syndrome, caused by fibrillin-1 mutations, are characterized by elevated cytokines and fragmentated elastic laminae in the aortic wall. This study explored whether and how specific fibrillin-1-regulated miRNAs mediate inflammatory cytokine expression and elastic laminae degradation in TAA. miRNA expression profiling at early and late TAA stages using a severe Marfan mouse model (Fbn1^mgR/mgR) revealed a spectrum of differentially regulated miRNAs. Bioinformatic analyses predicted the involvement of these miRNAs in inflammatory and extracellular matrix-related pathways. We demonstrate that upregulation of pro-inflammatory cytokines and matrix metalloproteinases is a common characteristic of mouse and human TAA tissues. miR-122, the most doCellular and molecular life sciences : CMLSFibrillin-1-regulated miR-122 has a critical role in thoracic aortic aneurysm formation.PMC11072253PJT-162099RGPIN-06278Muthu MLDinesh NEHReinhardt DPZhang RMKomarova STiedemann KRamkhelawon BfalseFibrillin-1-regulated miR-122 has a critical role in thoracic aortic aneurysm formation.Thoracic aortic aneurysms (TAA) in Marfan syndrome, caused by fibrillin-1 mutations, are characterized by elevated cytokines and fragmentated elastic laminae in the aortic wall. This study explored whether and how specific fibrillin-1-regulated miRNAs mediate inflammatory cytokine expression and elastic laminae degradation in TAA. miRNA expression profiling at early and late TAA stages using a severe Marfan mouse model (Fbn1^mgR/mgR) revealed a spectrum of differentially regulated miRNAs. Bioinformatic analyses predicted the involvement of these miRNAs in inflammatory and extracellular matrix-related pathways. We demonstrate that upregulation of pro-inflammatory cytokines and matrix metalloproteinases is a common characteristic of mouse and human TAA tissues. miR-122, the most do2022-01-01T00:00:00Z2022 May2026-06-01T20:26:06.63Z2026-05-22T03:07:44.052ZS-EPMC110722533560654710.1007/s00018-022-04337-8