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Increased reactive oxygen species (ROS) production and inflammation are key factors in the pathogenesis of atherosclerosis. We previously reported that NOX activator 1 (NOXA1) is the critical functional homolog of p67phox for NADPH oxidase activation in mouse vascular smooth muscle cells (VSMC). Here we investigated the effects of systemic and SMC-specific deletion of Noxa1 on VSMC phenotype during atherogenesis in mice. Neointimal hyperplasia following endovascular injury was lower in Noxa1-deficient mice versus the wild-type following endovascular injury. Noxa1 deletion in Apoe-/- or Ldlr-/- mice fed a Western diet showed 50% reduction in vascular ROS and 30% reduction in aortic atherosclerotic lesion area and aortic sinus lesion volume (P < 0.01). SMC-specific deletion of Noxa1 in Apoe-/- mice (Noxa1SMC-/-/Apoe-/-) similarly decreased vascular ROS levels and atherosclerotic lesion size. TNFα-induced ROS generation, proliferation and migration were significantly attenuated in Noxa1-deficient versus wild-type VSMC. Immunofluorescence analysis of atherosclerotic lesions showed a significant decrease in cells positive for CD68 and myosin11 (22% versus 9%) and Mac3 and α-actin (17% versus 5%) in the Noxa1SMC-/-/Apoe-/- versus Apoe-/- mice. The expression of transcription factor KLF4, a modulator of VSMC phenotype, and its downstream targets - VCAM1, CCL2, and MMP2 - were significantly reduced in the lesions of Noxa1SMC-/-/Apoe-/- versus Apoe-/- mice as well as in oxidized phospholipids treated Noxa1SMC-/- versus wild-type VSMC. Our data support an important role for NOXA1-dependent NADPH oxidase activity in VSMC plasticity during restenosis and atherosclerosis, augmenting VSMC proliferation and migration and KLF4-mediated transition to macrophage-like cells, plaque inflammation, and expansion.
Pubmed ID: 30576919
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Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
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View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
View all literature mentionsCommercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
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View all literature mentionsAmerican chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.
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View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name B6.129P2-Apoetm1Unc/J from IMSR.
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