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Proteomic Alterations Associated with Biomechanical Dysfunction are Early Processes in the Emilin1 Deficient Mouse Model of Aortic Valve Disease
- Source :
- Annals of Biomedical Engineering. 45:2548-2562
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Aortic valve (AV) disease involves stiffening of the AV cusp with progression characterized by inflammation, fibrosis, and calcification. Here, we examine the relationship between biomechanical valve function and proteomic changes before and after the development of AV pathology in the Emilin1−/− mouse model of latent AV disease. Biomechanical studies were performed to quantify tissue stiffness at the macro (micropipette) and micro (atomic force microscopy (AFM)) levels. Micropipette studies showed that the Emilin1−/− AV annulus and cusp regions demonstrated increased stiffness only after the onset of AV disease. AFM studies showed that the Emilin1−/− cusp stiffens before the onset of AV disease and worsens with the onset of disease. Proteomes from AV cusps were investigated to identify protein functions, pathways, and interaction network alterations that occur with age- and genotype-related valve stiffening. Protein alterations due to Emilin1 deficiency, including changes in pathways and functions, preceded biomechanical aberrations, resulting in marked depletion of extracellular matrix (ECM) proteins interacting with TGFB1, including latent transforming growth factor beta 3 (LTBP3), fibulin 5 (FBLN5), and cartilage intermediate layer protein 1 (CILP1). This study identifies proteomic dysregulation is associated with biomechanical dysfunction as early pathogenic processes in the Emilin1−/− model of AV disease.
- Subjects :
- Heart Defects, Congenital
Male
Proteomics
0301 basic medicine
Aortic valve
Pathology
medicine.medical_specialty
Heart Valve Diseases
Biomedical Engineering
030204 cardiovascular system & hematology
Article
Transforming Growth Factor beta1
Extracellular matrix
03 medical and health sciences
0302 clinical medicine
Bicuspid Aortic Valve Disease
Fibrosis
medicine
Animals
Mice, Knockout
Extracellular Matrix Proteins
Membrane Glycoproteins
Chemistry
EMILIN1
medicine.disease
Biomechanical Phenomena
Fibulin
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Transforming growth factor, beta 3
Aortic Valve
FBLN5
cardiovascular system
Female
Calcification
Subjects
Details
- ISSN :
- 15739686 and 00906964
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- Annals of Biomedical Engineering
- Accession number :
- edsair.doi.dedup.....dc847d6e1ab3fc7159ce1780431c1945