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High serum thrombospondin-1 concentration is associated with slower abdominal aortic aneurysm growth and deficiency of thrombospondin-1 promotes angiotensin II induced aortic aneurysm in mice
- Source :
- Clinical Science (London, England : 1979)
- Publication Year :
- 2017
- Publisher :
- Portland Press Ltd., 2017.
-
Abstract
- Abdominal aortic aneurysm (AAA) is a common age-related vascular disease characterized by progressive weakening and dilatation of the aortic wall. Thrombospondin-1 (TSP-1; gene Thbs1) is a member of the matricellular protein family important in the control of extracellular matrix (ECM) remodelling. In the present study, the association of serum TSP-1 concentration with AAA progression was assessed in 276 men that underwent repeated ultrasound for a median 5.5 years. AAA growth was negatively correlated with serum TSP-1 concentration (Spearman’s rho −0.129, P=0.033). Men with TSP-1 in the highest quartile had a reduced likelihood of AAA growth greater than median during follow-up (OR: 0.40; 95% confidence interval (CI): 0.19–0.84, P=0.016, adjusted for other risk factors). Immunohistochemical staining for TSP-1 was reduced in AAA body tissues compared with the relatively normal AAA neck. To further assess the role of TSP-1 in AAA initiation and progression, combined TSP-1 and apolipoprotein deficient (Thbs1−/−ApoE−/−, n=20) and control mice (ApoE−/−, n=20) were infused subcutaneously with angiotensin II (AngII) for 28 days. Following AngII infusion, Thbs1−/− ApoE−/− mice had larger AAAs by ultrasound (P=0.024) and ex vivo morphometry measurement (P=0.006). The Thbs1−/−ApoE−/− mice also showed increased elastin filament degradation along with elevated systemic levels and aortic expression of matrix metalloproteinase (MMP)-9. Suprarenal aortic segments and vascular smooth muscle cells (VSMCs) isolated from Thbs1−/−ApoE−/− mice showed reduced collagen 3A1 gene expression. Furthermore, Thbs1−/−ApoE−/− mice had reduced aortic expression of low-density lipoprotein (LDL) receptor-related protein 1. Collectively, findings from the present study suggest that TSP-1 deficiency promotes maladaptive remodelling of the ECM leading to accelerated AAA progression.
- Subjects :
- Male
0301 basic medicine
Time Factors
Apolipoprotein B
030204 cardiovascular system & hematology
Thrombospondin 1
Aortic aneurysm
0302 clinical medicine
immune system diseases
Risk Factors
Odds Ratio
cytokine
vascular inflammation
Aorta, Abdominal
Cells, Cultured
Ultrasonography
Mice, Knockout
biology
Angiotensin II
Matricellular protein
virus diseases
General Medicine
Abdominal aortic aneurysm
Phenotype
Matrix Metalloproteinase 9
Chemokine
Disease Progression
cardiovascular system
Low Density Lipoprotein Receptor-Related Protein-1
endocrine system
medicine.medical_specialty
Vascular Remodeling
03 medical and health sciences
Apolipoproteins E
Commentaries
Internal medicine
medicine
Animals
Humans
Genetic Predisposition to Disease
cardiovascular diseases
business.industry
Tumor Suppressor Proteins
medicine.disease
Elastin
Surgery
Disease Models, Animal
Collagen Type III
030104 developmental biology
Endocrinology
Receptors, LDL
Proteolysis
Commentary
biology.protein
business
Biomarkers
Aortic Aneurysm, Abdominal
Lipoprotein
Subjects
Details
- ISSN :
- 14708736 and 01435221
- Volume :
- 131
- Database :
- OpenAIRE
- Journal :
- Clinical Science
- Accession number :
- edsair.doi.dedup.....cd9c299517f039c75c9b9c60fb1d697c