Glycocalyx-targeted therapy ameliorates age-related arterial dysfunction.

Autor: Machin DR; Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA. dmachin@fsu.edu.; Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, FL, 32306, USA. dmachin@fsu.edu., Trott DW; Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA., Gogulamudi VR; Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA., Islam MT; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA., Bloom SI; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA., Vink H; Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands.; MicroVascular Health Solutions LLC, Alpine, UT, USA., Lesniewski LA; Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA.; VA Salt Lake City, GRECC, Salt Lake City, UT, USA., Donato AJ; Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA.; VA Salt Lake City, GRECC, Salt Lake City, UT, USA.; Department of Biochemistry, University of Utah, Salt Lake City, UT, USA.
Jazyk: angličtina
Zdroj: GeroScience [Geroscience] 2023 Aug; Vol. 45 (4), pp. 2351-2365. Date of Electronic Publication: 2023 Feb 14.
DOI: 10.1007/s11357-023-00745-1
Abstrakt: Advanced age is accompanied by arterial dysfunction, as well as a diminished glycocalyx, which may be linked to reduced high molecular weight-hyaluronan (HMW-HA) synthesis. However, the impact of glycocalyx deterioration in age-related arterial dysfunction is unknown. We sought to determine if manipulations in glycocalyx properties would alter arterial function. Tamoxifen-induced hyaluronan synthase 2 (Has2) reduction was used to decrease glycocalyx properties. Three weeks post-tamoxifen treatment, glycocalyx thickness was lower in Has2 knockout compared to wild-type mice (P<0.05). Has2 reduction induced arterial dysfunction, demonstrated by impaired endothelium-dependent dilation (EDD) and elevated aortic stiffness (P<0.05). To augment glycocalyx properties, old mice received 10 weeks of a glycocalyx-targeted therapy via Endocalyx™ (old+ECX), which contains HMW-HA and other glycocalyx components. Compared to old control mice, glycocalyx properties and EDD were augmented, and aortic stiffness decreased in old+ECX mice (P<0.05). Old+ECX mice had a more youthful aortic phenotype, demonstrated by lower collagen content and higher elastin content than old control mice (P<0.05). Functional outcomes were repeated in old mice that underwent a diet supplemented solely with HMW-HA (old+HA). Compared to old controls, glycocalyx properties and EDD were augmented, and aortic stiffness was lower in old+HA mice (P<0.05). We did not observe any differences between old+HA and old+ECX mice (P>0.05). Has2 reduction phenocopies age-related arterial dysfunction, while 10 weeks of glycocalyx-targeted therapy that restores the glycocalyx also ameliorates age-related arterial dysfunction. These findings suggest that the glycocalyx may be a viable therapeutic target to ameliorate age-related arterial dysfunction.
(© 2023. The Author(s), under exclusive licence to American Aging Association.)
Databáze: MEDLINE
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