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Elastic tissue disruption is a major pathogenic factor to human vascular disease.
- Source :
-
Molecular biology reports [Mol Biol Rep] 2021 May; Vol. 48 (5), pp. 4865-4878. Date of Electronic Publication: 2021 Jun 15. - Publication Year :
- 2021
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Abstract
- Elastic fibers are essential components of the arterial extracellular matrix. They consist of the protein elastin and an array of microfibrils that support the protein and connect it to the surrounding matrix. The elastin gene encodes tropoelastin, a protein that requires extensive cross-linking to become elastin. Tropoelastin is expressed throughout human life, but its expression levels decrease with age, suggesting that the potential to synthesize elastin persists during lifetime although declines with aging. The initial abnormality documented in human atherosclerosis is fragmentation and loss of the elastic network in the medial layer of the arterial wall, suggesting an imbalance between elastic fiber injury and restoration. Damaged elastic structures are not adequately repaired by synthesis of new elastic elements. Progressive collagen accumulation follows medial elastic fiber disruption and fibrous plaques are formed, but advanced atherosclerosis lesions do not develop in the absence of prior elastic injury. Aging is associated with arterial extracellular matrix anomalies that evoke those present in early atherosclerosis. The reduction of elastic fibers with subsequent collagen accumulation leads to arterial stiffening and intima-media thickening, which are independent predictors of incident hypertension in prospective community-based studies. Arterial stiffening precedes the development of hypertension. The fundamental role of the vascular elastic network to arterial structure and function is emphasized by congenital disorders caused by mutations that disrupt normal elastic fiber production. Molecular changes in the genes coding tropoelastin, lysyl oxidase (tropoelastin cross-linking), and elastin-associated microfibrils, including fibrillin-1, fibulin-4, and fibulin-5 produce severe vascular injury due to absence of functional elastin.
- Subjects :
- Aging physiology
Animals
Atherosclerosis pathology
Collagen metabolism
Congenital Abnormalities
Elastic Tissue cytology
Elastic Tissue metabolism
Elastin metabolism
Extracellular Matrix metabolism
Extracellular Matrix pathology
Fibrillins genetics
Fibrillins metabolism
Fibroblasts metabolism
Humans
Microfilament Proteins metabolism
Mutation
Protein-Lysine 6-Oxidase genetics
Protein-Lysine 6-Oxidase metabolism
Tropoelastin genetics
Tropoelastin metabolism
Vascular Stiffness physiology
Elastic Tissue pathology
Vascular Diseases metabolism
Vascular Diseases pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1573-4978
- Volume :
- 48
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular biology reports
- Publication Type :
- Academic Journal
- Accession number :
- 34129188
- Full Text :
- https://doi.org/10.1007/s11033-021-06478-8