D-4F reduces EO6 immunoreactivity, SREBP-1c mRNA levels, and renal inflammation in LDL receptor-null mice fed a Western diet
LDL receptor-null (LDLR−/−) mice on a Western diet (WD) develop endothelial dysfunction and atherosclerosis, which are improved by the apolipoprotein A-I (apoA-I) mimetic peptide D-4F. Focusing on the kidney, LDLR−/−mice were fed a WD with D-4F or the inactive control peptide scrambled D-4F (ScD-4F)...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2008-01-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520428949 |
| _version_ | 1819076964714020864 |
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| author | Georgette M. Buga Joy S. Frank Giuliano A. Mottino Ashkan Hakhamian Ajay Narasimha Andrew D. Watson Babak Yekta Mohamad Navab Srinivasa T. Reddy G.M. Anantharamaiah Alan M. Fogelman |
| author_facet | Georgette M. Buga Joy S. Frank Giuliano A. Mottino Ashkan Hakhamian Ajay Narasimha Andrew D. Watson Babak Yekta Mohamad Navab Srinivasa T. Reddy G.M. Anantharamaiah Alan M. Fogelman |
| author_sort | Georgette M. Buga |
| collection | DOAJ |
| description | LDL receptor-null (LDLR−/−) mice on a Western diet (WD) develop endothelial dysfunction and atherosclerosis, which are improved by the apolipoprotein A-I (apoA-I) mimetic peptide D-4F. Focusing on the kidney, LDLR−/−mice were fed a WD with D-4F or the inactive control peptide scrambled D-4F (ScD-4F) added to their drinking water. The control mice (ScD-4F) developed glomerular changes, increased immunostaining for MCP-1/CCL2 chemokine, increased macrophage CD68 and F4/80 antigens, and increased oxidized phospholipids recognized by the EO6 monoclonal antibody in both glomerular and tublo-interstitial areas. All of these parameters were significantly reduced by D-4F treatment, approaching levels found in wild-type C57BL/6J or LDLR−/− mice fed a chow diet. Sterol-regulatory element binding protein-1c (SREBP-1c) mRNA levels and triglyceride levels were elevated in the kidneys of the control mice (ScD-4F) fed the WD compared with C57BL/6J and LDLR−/− mice on chow (P < 0.001 and P < 0.001, respectively) and compared with D-4F-treated mice on the WD (P < 0.01). There was no significant difference in plasma lipids, lipoproteins, glucose, blood pressure, or renal apoB levels between D-4F- and ScD-4F-treated mice. We conclude that D-4F reduced renal oxidized phospholipids, resulting in lower expression of SREBP-1c, which, in turn, resulted in lower triglyceride content and reduced renal inflammation. |
| first_indexed | 2024-12-21T18:49:40Z |
| format | Article |
| id | doaj.art-e3f7b5045c0846d1955579e0797839f7 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-21T18:49:40Z |
| publishDate | 2008-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-e3f7b5045c0846d1955579e0797839f72022-12-21T18:53:48ZengElsevierJournal of Lipid Research0022-22752008-01-01491192205D-4F reduces EO6 immunoreactivity, SREBP-1c mRNA levels, and renal inflammation in LDL receptor-null mice fed a Western dietGeorgette M. Buga0Joy S. Frank1Giuliano A. Mottino2Ashkan Hakhamian3Ajay Narasimha4Andrew D. Watson5Babak Yekta6Mohamad Navab7Srinivasa T. Reddy8G.M. Anantharamaiah9Alan M. Fogelman10Department of Medicine, David Geffen School of Medicine at the University of California–Los Angeles, Los Angeles, CA 90095-1679Department of Medicine, David Geffen School of Medicine at the University of California–Los Angeles, Los Angeles, CA 90095-1679Department of Medicine, David Geffen School of Medicine at the University of California–Los Angeles, Los Angeles, CA 90095-1679Department of Medicine, David Geffen School of Medicine at the University of California–Los Angeles, Los Angeles, CA 90095-1679Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California–Los Angeles, Los Angeles, CA 90095-1679Department of Medicine, David Geffen School of Medicine at the University of California–Los Angeles, Los Angeles, CA 90095-1679Department of Medicine, David Geffen School of Medicine at the University of California–Los Angeles, Los Angeles, CA 90095-1679Department of Medicine, David Geffen School of Medicine at the University of California–Los Angeles, Los Angeles, CA 90095-1679Department of Medicine, David Geffen School of Medicine at the University of California–Los Angeles, Los Angeles, CA 90095-1679; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California–Los Angeles, Los Angeles, CA 90095-1679The Atherosclerosis Research Unit, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294Department of Medicine, David Geffen School of Medicine at the University of California–Los Angeles, Los Angeles, CA 90095-1679LDL receptor-null (LDLR−/−) mice on a Western diet (WD) develop endothelial dysfunction and atherosclerosis, which are improved by the apolipoprotein A-I (apoA-I) mimetic peptide D-4F. Focusing on the kidney, LDLR−/−mice were fed a WD with D-4F or the inactive control peptide scrambled D-4F (ScD-4F) added to their drinking water. The control mice (ScD-4F) developed glomerular changes, increased immunostaining for MCP-1/CCL2 chemokine, increased macrophage CD68 and F4/80 antigens, and increased oxidized phospholipids recognized by the EO6 monoclonal antibody in both glomerular and tublo-interstitial areas. All of these parameters were significantly reduced by D-4F treatment, approaching levels found in wild-type C57BL/6J or LDLR−/− mice fed a chow diet. Sterol-regulatory element binding protein-1c (SREBP-1c) mRNA levels and triglyceride levels were elevated in the kidneys of the control mice (ScD-4F) fed the WD compared with C57BL/6J and LDLR−/− mice on chow (P < 0.001 and P < 0.001, respectively) and compared with D-4F-treated mice on the WD (P < 0.01). There was no significant difference in plasma lipids, lipoproteins, glucose, blood pressure, or renal apoB levels between D-4F- and ScD-4F-treated mice. We conclude that D-4F reduced renal oxidized phospholipids, resulting in lower expression of SREBP-1c, which, in turn, resulted in lower triglyceride content and reduced renal inflammation.http://www.sciencedirect.com/science/article/pii/S0022227520428949atherosclerosisapolipoprotein A-I mimetic peptidesHDLhyperlipidemiakidneylipoproteins |
| spellingShingle | Georgette M. Buga Joy S. Frank Giuliano A. Mottino Ashkan Hakhamian Ajay Narasimha Andrew D. Watson Babak Yekta Mohamad Navab Srinivasa T. Reddy G.M. Anantharamaiah Alan M. Fogelman D-4F reduces EO6 immunoreactivity, SREBP-1c mRNA levels, and renal inflammation in LDL receptor-null mice fed a Western diet Journal of Lipid Research atherosclerosis apolipoprotein A-I mimetic peptides HDL hyperlipidemia kidney lipoproteins |
| title | D-4F reduces EO6 immunoreactivity, SREBP-1c mRNA levels, and renal inflammation in LDL receptor-null mice fed a Western diet |
| title_full | D-4F reduces EO6 immunoreactivity, SREBP-1c mRNA levels, and renal inflammation in LDL receptor-null mice fed a Western diet |
| title_fullStr | D-4F reduces EO6 immunoreactivity, SREBP-1c mRNA levels, and renal inflammation in LDL receptor-null mice fed a Western diet |
| title_full_unstemmed | D-4F reduces EO6 immunoreactivity, SREBP-1c mRNA levels, and renal inflammation in LDL receptor-null mice fed a Western diet |
| title_short | D-4F reduces EO6 immunoreactivity, SREBP-1c mRNA levels, and renal inflammation in LDL receptor-null mice fed a Western diet |
| title_sort | d 4f reduces eo6 immunoreactivity srebp 1c mrna levels and renal inflammation in ldl receptor null mice fed a western diet |
| topic | atherosclerosis apolipoprotein A-I mimetic peptides HDL hyperlipidemia kidney lipoproteins |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520428949 |
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