دورية أكاديمية
Effect of new thiazolidine derivatives LPSF/GQ-02 and LPSF/GQ-16 on atherosclerotic lesions in LDL receptor-deficient mice (LDLR(-/-)).
| العنوان: | Effect of new thiazolidine derivatives LPSF/GQ-02 and LPSF/GQ-16 on atherosclerotic lesions in LDL receptor-deficient mice (LDLR(-/-)). |
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| المؤلفون: | Soares E Silva AK; Laboratório de Ultraestrutura, Centro de Pesquisa Aggeu Magalhães, FIOCRUZ, Recife, Brazil. kls.amanda@gmail.com, de Oliveira Cipriano Torres D, Santos Rocha SW, dos Santos Gomes FO, dos Santos Silva B, Donato MA, Raposo C, Santos AC, de Lima Mdo C, Galdino SL, da Rocha Pitta I, de Souza JR, Peixoto CA |
| المصدر: | Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology [Cardiovasc Pathol] 2013 Jan-Feb; Vol. 22 (1), pp. 81-90. Date of Electronic Publication: 2012 Jul 15. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Pub. Co Country of Publication: United States NLM ID: 9212060 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1336 (Electronic) Linking ISSN: 10548807 NLM ISO Abbreviation: Cardiovasc Pathol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Elsevier Science Pub. Co., c1992- |
| مواضيع طبية MeSH: | Aorta/*drug effects , Aortic Diseases/*drug therapy , Atherosclerosis/*drug therapy , Cardiovascular Agents/*pharmacology , Receptors, LDL/*deficiency , Thiazolidinediones/*pharmacology , Thiazolidines/*pharmacology, Animals ; Aorta/metabolism ; Aorta/ultrastructure ; Aortic Diseases/genetics ; Aortic Diseases/pathology ; Apoptosis/drug effects ; Atherosclerosis/blood ; Atherosclerosis/genetics ; Atherosclerosis/pathology ; Blood Glucose/drug effects ; Blood Glucose/metabolism ; Blotting, Western ; Cardiovascular Agents/toxicity ; Disease Models, Animal ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/pathology ; Immunohistochemistry ; Insulin/blood ; Insulin Resistance ; Lipids/blood ; Matrix Metalloproteinase 9/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microscopy, Electron, Transmission ; Nitric Oxide Synthase Type III/metabolism ; Pioglitazone ; Plaque, Atherosclerotic ; Receptors, LDL/genetics ; Thiazolidinediones/toxicity ; Thiazolidines/toxicity ; Time Factors |
| مستخلص: | Background: Atherosclerotic cardiovascular disease is a chronic inflammatory condition. Thiazolidinediones (TZDs) are used to enhance sensitivity to insulin and have demonstrated a protective effect over a variety of cardiovascular markers and risk factors. Controversially, the TZDs are associated with the development of heart failure. Thus, lines of research have invested in the search for new molecules in order to obtain more selective and less harmful treatment alternatives for the pathogenesis of atherosclerosis and its risk factors. Methods: Animals were fed a diet rich in fat for 10 weeks. In the last 2 weeks, animals received either pioglitazone, LPSF/GQ-02, or LPSF/GQ-16 daily through gavage. At the end of the treatment, blood was collected for biochemical analysis and the aortas were dissected for subsequent analyses. Results: No changes in the blood lipid profile were found following the use of the drugs in comparison to the control. However, the new thiazolidine derivatives were more efficient in improving insulin resistance in comparison to pioglitazone and the control group. Morphometric analyses revealed that neither pioglitazone nor LPSF/GQ16 led to satisfactory effects over atherosclerosis. However, LPSF/GQ-02 led to a reduction in area of the atherosclerotic lesions. Ultrastructural analyses revealed extensive degeneration of the endothelium and an increase in apoptotic cells in the subendothelial space following the use of pioglitazone and LPSF/GQ-16. However, LPSF/GQ-02 caused minimal cell alterations in the aortic endothelium. Regarding markers, endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase 9 (MMP-9), LPSF/GQ-16, and pioglitazone exerted similar effects, increasing the expression of MMP-9, and had no effect on the expression of eNOS compared with the control group. On the other hand, LPSF/GQ-02 was effective in reducing the expression of MMP-9 and increased eNOS significantly. Conclusions: The results suggest that the new thiazolidine derivative LPSF/GQ-02 is a promising candidate for the treatment of atherosclerosis. (Copyright © 2013 Elsevier Inc. All rights reserved.) |
| المشرفين على المادة: | 0 (5-(4-chlorobenzylidene)-3-(4-methylbenzyl)thiazolidine-2,4-dione) 0 (5-(5-bromo-2-methoxybenzylidene)-3-(4-methyl-benzyl)thiazolidine-2,4-dione) 0 (Blood Glucose) 0 (Cardiovascular Agents) 0 (Insulin) 0 (Lipids) 0 (Receptors, LDL) 0 (Thiazolidinediones) 0 (Thiazolidines) EC 1.14.13.39 (Nitric Oxide Synthase Type III) EC 1.14.13.39 (Nos3 protein, mouse) EC 3.4.24.35 (Matrix Metalloproteinase 9) EC 3.4.24.35 (Mmp9 protein, mouse) X4OV71U42S (Pioglitazone) |
| تواريخ الأحداث: | Date Created: 20120717 Date Completed: 20130528 Latest Revision: 20181202 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.carpath.2012.05.006 |
| PMID: | 22795892 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1879-1336 |
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| DOI: | 10.1016/j.carpath.2012.05.006 |