1. Physiological Impact of a Synthetic Elastic Protein in Arterial Diseases Related to Alterations of Elastic Fibers: Effect on the Aorta of Elastin-Haploinsufficient Male and Female Mice
- Author
-
Quentin Boëté, Ming Lo, Kiao-Ling Liu, Guillaume Vial, Emeline Lemarié, Maxime Rougelot, Iris Steuckardt, Olfa Harki, Axel Couturier, Jonathan Gaucher, Sophie Bouyon, Alexandra Demory, Antoine Boutin-Paradis, Naima El Kholti, Aurore Berthier, Jean-Louis Pépin, Anne Briançon-Marjollet, Elise Lambert, Romain Debret, and Gilles Faury
- Subjects
aorta ,structure ,mechanics ,reactivity ,elastic fiber synthesis/repair ,pharmacotherapy ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Elastic fibers, made of elastin (90%) and fibrillin-rich microfibrils (10%), are the key extracellular components, which endow the arteries with elasticity. The alteration of elastic fibers leads to cardiovascular dysfunctions, as observed in elastin haploinsufficiency in mice (Eln+/-) or humans (supravalvular aortic stenosis or Williams–Beuren syndrome). In Eln+/+ and Eln+/- mice, we evaluated (arteriography, histology, qPCR, Western blots and cell cultures) the beneficial impact of treatment with a synthetic elastic protein (SEP), mimicking several domains of tropoelastin, the precursor of elastin, including hydrophobic elasticity-related domains and binding sites for elastin receptors. In the aorta or cultured aortic smooth muscle cells from these animals, SEP treatment induced a synthesis of elastin and fibrillin-1, a thickening of the aortic elastic lamellae, a decrease in wall stiffness and/or a strong trend toward a reduction in the elastic lamella disruptions in Eln+/- mice. SEP also modified collagen conformation and transcript expressions, enhanced the aorta constrictive response to phenylephrine in several animal groups, and, in female Eln+/- mice, it restored the normal vasodilatory response to acetylcholine. SEP should now be considered as a biomimetic molecule with an interesting potential for future treatments of elastin-deficient patients with altered arterial structure/function.
- Published
- 2022
- Full Text
- View/download PDF