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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.

Type

Journal article

Journal

Journal of molecular and cellular cardiology

Publication Date

01/2013

Volume

54

Pages

65 - 72

Addresses

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.

Keywords

Muscle, Smooth, Vascular, Cells, Cultured, Mitochondria, Muscle, Myocytes, Smooth Muscle, Animals, Mice, Knockout, Humans, Mice, Carotid Artery Diseases, Mitochondrial Proton-Translocating ATPases, Aldehyde Dehydrogenase, Annexin A1, Mitochondrial Proteins, Proteome, Cytokines, Proteomics, Gene Expression, Oxidation-Reduction, Phenotype, Principal Component Analysis, Adult, Atherosclerosis, Peroxiredoxins