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Elastic tissue disruption is a major pathogenic factor to human vascular disease

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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.

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Acknowledgements

We wish to thank Ms. Gema Souto, MHS for her continuing support.

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Authors and Affiliations

  1. Nephrology Division, Internal Medicine Department, Hospital General Juan Cardona, c/ Pardo Bazán s/n, 15406, Ferrol, Spain

    María M. Adeva-Andany, Carlos Fernández-Fernández, Manuel González-Lucán & Raquel Funcasta-Calderón

  2. University of Santiago de Compostela Medical School, Santiago de Compostela, Spain

    Lucía Adeva-Contreras

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  1. María M. Adeva-Andany
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MAA and LAC had the idea of the article, performed the literature search and drafted the manuscript. MAA, CFF, MGL, and RFC performed the data analysis. All authors critically revised the work for important intellectual content. All authors read and approved the final version of the manuscript.

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Adeva-Andany, M.M., Adeva-Contreras, L., Fernández-Fernández, C. et al. Elastic tissue disruption is a major pathogenic factor to human vascular disease. Mol Biol Rep 48, 4865–4878 (2021). https://doi.org/10.1007/s11033-021-06478-8

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