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Keywords {🔍}

glp, plaque, sitagliptin, article, mice, content, aortic, pubmed, google, scholar, dppiv, cas, diabetes, effects, mmp, macrophage, lesions, treatment, patients, type, migration, collagen, human, levels, root, arch, controls, size, monocyte, cell, cells, study, apoe, inhibition, fig, lesion, germany, highfat, diet, monocytes, glucose, shown, data, reduces, inhibitors, dipeptidyl, peptide, atherosclerosis, activity, glucagonlike,

Topics {✒️}

3 mg h-gly-pro-p-nitroaniline dpp-iv inhibitors des-fluoro-sitagliptin cd26/dipeptidyl-peptidase iv glucose/kg body weight drugs inhibit dpp-iv reduced monocyte/macrophage infiltration dpp-iv activity measurement inhibiting dpp-iv activity western blot analysis dpp-iv inhibitors influence class-matched igg served polyvinylpyrrolidone-free polycarbonate membrane chemokine-induced monocyte migration dpp-iv enzymatic activity plaque monocyte/macrophage content glucose-dependent insulinotropic polypeptide pi3k/akt-dependent pathways dpp-iv substrates include ddp-iv inhibitor treatment random high-power fields apolipoprotein e-deficient mice dpp-iv inhibitor treatment dpp-iv-inhibitor treatment cd8alpha-negative dendritic cells p-myosin light chain human monocyte-derived macrophages primary anti-mac3 antibody goat anti-macrophage-3 antigen des-fluoro-sitagliptin dipeptidyl peptidase-iv dipeptidyl peptidase activity dipeptidyl peptidase-4 inhibitor cell type-specific marker pancreatic beta cells enhancing insulin secretion macrophages reduces atherosclerosis chemokine-induced migration dyslipidemia inhibits toll research diets d12108 plaque macrophage content dpp iv/cd26 plaque macrophage infiltration dpp-iv activity influence vascular chemokine privacy choices/manage cookies dpp-iv inhibitors dpp-iv inhibitor low collagen content monocyte-derived macrophages macrophage mmp-9 production

Questions {❓}

• Geelhoed-Duijvestijn PH (2007) Incretins: a new treatment option for type 2 diabetes?

Schema {🗺️}

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         headline:Sitagliptin reduces plaque macrophage content and stabilises arteriosclerotic lesions in Apoe −/− mice
         description:Inhibitors of dipeptidyl peptidase-IV (DPP-IV), such as sitagliptin, increase glucagon-like peptide-1 (GLP-1) concentrations and are current treatment options for patients with type 2 diabetes mellitus. As patients with diabetes exhibit a high risk of developing severe atherosclerosis, we investigated the effect of sitagliptin on atherogenesis in Apoe −/− mice. Apoe −/− mice were fed a high-fat diet and treated with either sitagliptin or placebo for 12 weeks. Plaque size and plaque composition were analysed using Oil Red O staining and immunohistochemistry. Furthermore, in vitro experiments with the modified Boyden chamber and with gelatine zymography were performed to analyse the effects of GLP-1 on isolated human monocyte migration and metalloproteinase-9 (MMP-9) release. Treatment of Apoe −/− mice with sitagliptin significantly reduced plaque macrophage infiltration (the aortic root and aortic arch both showing a 67% decrease; p < 0.05) and plaque MMP-9 levels (aortic root showing a 69% and aortic arch a 58% reduction; both p < 0.01) compared with controls. Moreover, sitagliptin significantly increased plaque collagen content more than twofold (aortic root showing an increase of 58% and aortic arch an increase of 73%; both p < 0.05) compared with controls but did not change overall lesion size (8.1 ± 3.5% vs 5.1 ± 2.5% for sitagliptin vs controls; p = NS). In vitro, pretreatment of isolated human monocytes with GLP-1 significantly decreased cell migration induced by both monocyte chemotactic protein-1 and by the protein known as regulated on activation, normal T cell expressed and secreted (RANTES) in a concentration-dependent manner. Furthermore, GLP-1 significantly decreased MMP-9 release from isolated human monocyte-derived macrophages. Sitagliptin reduces plaque inflammation and increases plaque stability, potentially by GLP-1-mediated inhibition of chemokine-induced monocyte migration and macrophage MMP-9 release. The effects observed may provide potential mechanisms for how DPP-IV inhibitors could modulate vascular disease in high-risk patients with type 2 diabetes mellitus.
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            Incretins
            Plaque stability
            Type 2 diabetes
            Internal Medicine
            Metabolic Diseases
            Human Physiology
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      headline:Sitagliptin reduces plaque macrophage content and stabilises arteriosclerotic lesions in Apoe −/− mice
      description:Inhibitors of dipeptidyl peptidase-IV (DPP-IV), such as sitagliptin, increase glucagon-like peptide-1 (GLP-1) concentrations and are current treatment options for patients with type 2 diabetes mellitus. As patients with diabetes exhibit a high risk of developing severe atherosclerosis, we investigated the effect of sitagliptin on atherogenesis in Apoe −/− mice. Apoe −/− mice were fed a high-fat diet and treated with either sitagliptin or placebo for 12 weeks. Plaque size and plaque composition were analysed using Oil Red O staining and immunohistochemistry. Furthermore, in vitro experiments with the modified Boyden chamber and with gelatine zymography were performed to analyse the effects of GLP-1 on isolated human monocyte migration and metalloproteinase-9 (MMP-9) release. Treatment of Apoe −/− mice with sitagliptin significantly reduced plaque macrophage infiltration (the aortic root and aortic arch both showing a 67% decrease; p < 0.05) and plaque MMP-9 levels (aortic root showing a 69% and aortic arch a 58% reduction; both p < 0.01) compared with controls. Moreover, sitagliptin significantly increased plaque collagen content more than twofold (aortic root showing an increase of 58% and aortic arch an increase of 73%; both p < 0.05) compared with controls but did not change overall lesion size (8.1 ± 3.5% vs 5.1 ± 2.5% for sitagliptin vs controls; p = NS). In vitro, pretreatment of isolated human monocytes with GLP-1 significantly decreased cell migration induced by both monocyte chemotactic protein-1 and by the protein known as regulated on activation, normal T cell expressed and secreted (RANTES) in a concentration-dependent manner. Furthermore, GLP-1 significantly decreased MMP-9 release from isolated human monocyte-derived macrophages. Sitagliptin reduces plaque inflammation and increases plaque stability, potentially by GLP-1-mediated inhibition of chemokine-induced monocyte migration and macrophage MMP-9 release. The effects observed may provide potential mechanisms for how DPP-IV inhibitors could modulate vascular disease in high-risk patients with type 2 diabetes mellitus.
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         Atherosclerosis
         Glucagon-like peptide-1
         Incretins
         Plaque stability
         Type 2 diabetes
         Internal Medicine
         Metabolic Diseases
         Human Physiology
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