title: Smooth muscle cells in human atherosclerosis: proteomic profiling reveals differences in expression of Annexin A1 and mitochondrial proteins in carotid disease.
abstract: Smooth muscle cells (SMC) contribute to the development and stability of atherosclerotic lesions. The molecular mechanisms that mediate their properties are incompletely defined. We employed proteomics and in vitro functional assays to identify the unique characteristics of intimal SMC isolated from human carotid endarterectomy specimens and medial SMC from thoracic aortas and carotids. We verified our findings in the Tampere Vascular Study. Human atheroma-derived SMC exhibit decreased expression of mitochondrial proteins ATP Synthase subunit-beta and Aldehyde dehydrogenase 2, and decreased mitochondrial activity when compared to control SMC. Moreover, a comparison between plaque-derived SMC isolated from patients with or without recent acute cerebrovascular symptoms uncovered an increase in Annexin A1, an endogenous anti-inflammatory protein, in the asymptomatic group. The deletion of Annexin A1 or the blockade of its signaling in SMC resulted in increased cytokine production at baseline and after stimulation with the pro-inflammatory cytokine Tumor Necrosis Factor α. In summary, our proteomics and biochemical analysis revealed mitochondrial damage in human plaque-derived SMC as well as a role of Annexin A1 in reducing the production of pro-inflammatory mediators in SMC.
authors.affiliation: Kennedy Institute of Rheumatology, Kennedy Institute, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, 65 Aspenlea Road, W6 8LH London, United Kingdom.
authors.forename: Leena E
authors.initials: LE
authors.lastname: Viiri
authors.forename: Louise E
authors.initials: LE
authors.lastname: Full
authors.forename: Tina J
authors.initials: TJ
authors.lastname: Navin
authors.forename: Shajna
authors.initials: S
authors.lastname: Begum
authors.forename: Athanasios
authors.initials: A
authors.lastname: Didangelos
authors.forename: Nagore
authors.initials: N
authors.lastname: Astola
authors.forename: Rolf K
authors.initials: RK
authors.lastname: Berge
authors.forename: Ilkka
authors.initials: I
authors.lastname: Seppälä
authors.forename: Joseph
authors.initials: J
authors.lastname: Shalhoub
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Franklin
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Alun H
authors.initials: AH
authors.lastname: Davies
authors.forename: Robin
authors.initials: R
authors.lastname: Wait
authors.forename: Claudia
authors.initials: C
authors.lastname: Monaco
mesh_terms: D000328:Adult; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D017305:Annexin A1 / Q000378:metabolism*; D050197:Atherosclerosis / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000378:metabolism; D010641:Phenotype; D025341:Principal Component Analysis; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics
chemical_list: D017305:Annexin A1; D016207:Cytokines; D024101:Mitochondrial Proteins; D020543:Proteome; D054464:Peroxiredoxins; C515029:ALDH2 protein, mouse; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C530489:ATP5b protein, mouse; D025261:Mitochondrial Proton-Translocating ATPases