Downregulation of the Proinflammatory State of Circulating Mononuclear Cells by Short-Term Treatment with Pioglitazone in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease
Background. This study was performed to investigate the influence of a short-term treatment with pioglitazone versus placebo on inflammatory activation of mononuclear cells (mRNA expression/protein secretion of inflammatory markers). Methods and Results. Sixty-three patients with well-controlled typ...
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| Format: | Article |
| Language: | English |
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2011-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2011/647017 |
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| author | Andreas Pfützner Alexander Weise Elisabeth Pfützner-Riehn Georg Lübben Michael Morcos Efstrathios Karagiannis Matthias Weber Thomas Forst |
| author_facet | Andreas Pfützner Alexander Weise Elisabeth Pfützner-Riehn Georg Lübben Michael Morcos Efstrathios Karagiannis Matthias Weber Thomas Forst |
| author_sort | Andreas Pfützner |
| collection | DOAJ |
| description | Background. This study was performed to investigate the influence of a short-term treatment with pioglitazone versus placebo on inflammatory activation of mononuclear cells (mRNA expression/protein secretion of inflammatory markers).
Methods and Results. Sixty-three patients with well-controlled type 2 diabetes (52 males, 11 females, age (Mean ± SD): 66±7 yrs, disease duration: 6.6±9.6 yrs, HbA1c: 6.7±0.6%) were randomized to additional 45 mg of pioglitazone or placebo to their existing metformin and sulfonylurea therpay for four weeks in a double-blind study design. Protein risk marker levels (hsCRP, MMP-9, MCP-1, etc.) and the expression of NFκB subunits and NFκB-modulated cytokines from isolated peripheral monocyte/macrophages were determined at baseline and endpoint. There were no changes in HbA1c, but significant biomarker improvements were seen with pioglitazone only. The mRNA marker expression was downregulated by pioglitazone and further up-regulated with placebo (e.g., P105 pioglitazone: −19%/placebo: +6%, RelA: −20%/+2%, MMP−9: −36%/+9%, TNFα: −10%/+14%, P<0.05
between groups in all cases).
Conclusions. Pioglitazone very rapidly down-regulated the activated state of peripheral monocytes/macrophages as assessed by mRNA expression of NFκB and NFκB-modulated cytokines and decreased plasma levels of cardiovascular risk marker proteins independent of glycemic control. |
| format | Article |
| id | doaj-art-b8e5b104ec6341d68940b92a4001130e |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-b8e5b104ec6341d68940b92a4001130e2025-02-03T01:30:08ZengWileyPPAR Research1687-47571687-47652011-01-01201110.1155/2011/647017647017Downregulation of the Proinflammatory State of Circulating Mononuclear Cells by Short-Term Treatment with Pioglitazone in Patients with Type 2 Diabetes Mellitus and Coronary Artery DiseaseAndreas Pfützner0Alexander Weise1Elisabeth Pfützner-Riehn2Georg Lübben3Michael Morcos4Efstrathios Karagiannis5Matthias Weber6Thomas Forst7IKFE Institute for Clinical Research and Development, Research Laboratory, 55116 Mainz, GermanyIKFE Institute for Clinical Research and Development, Research Laboratory, 55116 Mainz, GermanyThe Department of Endocrinology and Metabolism, University Hospital of Mainz, 55131 Mainz, GermanyTakeda Pharma, Medical Department, 52066 Aachen, GermanyCardiology Center, Medical Department, 69120 Heidelberg, GermanyTakeda Pharma, Medical Department, 52066 Aachen, GermanyThe Department of Endocrinology and Metabolism, University Hospital of Mainz, 55131 Mainz, GermanyIKFE Institute for Clinical Research and Development, Research Laboratory, 55116 Mainz, GermanyBackground. This study was performed to investigate the influence of a short-term treatment with pioglitazone versus placebo on inflammatory activation of mononuclear cells (mRNA expression/protein secretion of inflammatory markers). Methods and Results. Sixty-three patients with well-controlled type 2 diabetes (52 males, 11 females, age (Mean ± SD): 66±7 yrs, disease duration: 6.6±9.6 yrs, HbA1c: 6.7±0.6%) were randomized to additional 45 mg of pioglitazone or placebo to their existing metformin and sulfonylurea therpay for four weeks in a double-blind study design. Protein risk marker levels (hsCRP, MMP-9, MCP-1, etc.) and the expression of NFκB subunits and NFκB-modulated cytokines from isolated peripheral monocyte/macrophages were determined at baseline and endpoint. There were no changes in HbA1c, but significant biomarker improvements were seen with pioglitazone only. The mRNA marker expression was downregulated by pioglitazone and further up-regulated with placebo (e.g., P105 pioglitazone: −19%/placebo: +6%, RelA: −20%/+2%, MMP−9: −36%/+9%, TNFα: −10%/+14%, P<0.05 between groups in all cases). Conclusions. Pioglitazone very rapidly down-regulated the activated state of peripheral monocytes/macrophages as assessed by mRNA expression of NFκB and NFκB-modulated cytokines and decreased plasma levels of cardiovascular risk marker proteins independent of glycemic control.http://dx.doi.org/10.1155/2011/647017 |
| spellingShingle | Andreas Pfützner Alexander Weise Elisabeth Pfützner-Riehn Georg Lübben Michael Morcos Efstrathios Karagiannis Matthias Weber Thomas Forst Downregulation of the Proinflammatory State of Circulating Mononuclear Cells by Short-Term Treatment with Pioglitazone in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease PPAR Research |
| title | Downregulation of the Proinflammatory State of Circulating Mononuclear Cells by Short-Term Treatment with Pioglitazone in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease |
| title_full | Downregulation of the Proinflammatory State of Circulating Mononuclear Cells by Short-Term Treatment with Pioglitazone in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease |
| title_fullStr | Downregulation of the Proinflammatory State of Circulating Mononuclear Cells by Short-Term Treatment with Pioglitazone in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease |
| title_full_unstemmed | Downregulation of the Proinflammatory State of Circulating Mononuclear Cells by Short-Term Treatment with Pioglitazone in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease |
| title_short | Downregulation of the Proinflammatory State of Circulating Mononuclear Cells by Short-Term Treatment with Pioglitazone in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease |
| title_sort | downregulation of the proinflammatory state of circulating mononuclear cells by short term treatment with pioglitazone in patients with type 2 diabetes mellitus and coronary artery disease |
| url | http://dx.doi.org/10.1155/2011/647017 |
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