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Fibroblast growth factor 21 deletion aggravates diabetes-induced pathogenic changes in the aorta in type 1 diabetic mice.
- Source :
-
Cardiovascular diabetology [Cardiovasc Diabetol] 2015 Jun 11; Vol. 14 (1), pp. 77. Date of Electronic Publication: 2015 Jun 11. - Publication Year :
- 2015
-
Abstract
- Fibroblast growth factor 21 (FGF21) is an important regulator in glucose and lipid metabolism, and has been considered as a potential therapy for diabetes. The effect of FGF21 on the development and progression of diabetes-induced pathogenic changes in the aorta has not currently been addressed. To characterize these effects, type 1 diabetes was induced in both FGF21 knockout (FGF21KO) and C57BL/6 J wild type (WT) mice via multiple-dose streptozotocin injection. FGF21KO diabetic mice showed both earlier and more severe aortic remodeling indicated by aortic thickening, collagen accumulation and fibrotic mediator connective tissue growth factor expression. This was accompanied by significant aortic cell apoptosis than in WT diabetic mice. Further investigation found that FGF21 deletion exacerbated aortic inflammation and oxidative stress reflected by elevated expression of tumor necrosis factor α and transforming growth factor β, and the accumulation of 3-nitrotyrocine and 4-Hydroxynonenal. FGF21 administration can reverse the pathologic changes in FGF21KO diabetic mice. These findings demonstrate that FGF21 deletion aggravates aortic remodeling and cell death probably via exacerbation of aortic inflammation and oxidative stress. This marks FGF21 as a potential therapy for the treatment of aortic damage due to diabetes.
- Subjects :
- Aldehydes metabolism
Animals
Aorta pathology
Aortic Diseases genetics
Aortic Diseases pathology
Aortic Diseases prevention & control
Apoptosis
Collagen metabolism
Connective Tissue Growth Factor metabolism
Diabetes Mellitus, Experimental drug therapy
Diabetes Mellitus, Experimental genetics
Diabetes Mellitus, Experimental metabolism
Diabetes Mellitus, Type 1 drug therapy
Diabetes Mellitus, Type 1 genetics
Diabetes Mellitus, Type 1 metabolism
Diabetic Angiopathies genetics
Diabetic Angiopathies pathology
Diabetic Angiopathies prevention & control
Fibroblast Growth Factors administration & dosage
Fibroblast Growth Factors genetics
Fibrosis
Genetic Predisposition to Disease
Male
Mice, Inbred C57BL
Mice, Knockout
Nitric Oxide Synthase Type III metabolism
Oxidative Stress
Phenotype
Signal Transduction
Time Factors
Transforming Growth Factor beta metabolism
Tumor Necrosis Factor-alpha metabolism
Tyrosine analogs & derivatives
Tyrosine metabolism
Aorta metabolism
Aortic Diseases metabolism
Diabetes Mellitus, Experimental complications
Diabetes Mellitus, Type 1 complications
Diabetic Angiopathies metabolism
Fibroblast Growth Factors deficiency
Gene Deletion
Vascular Remodeling
Subjects
Details
- Language :
- English
- ISSN :
- 1475-2840
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cardiovascular diabetology
- Publication Type :
- Academic Journal
- Accession number :
- 27391008
- Full Text :
- https://doi.org/10.1186/s12933-015-0241-0