Autor: |
Gioscia-Ryan RA; Department of Integrative Physiology, University of Colorado, Boulder, Boulder, Colorado., Battson ML; Department of Integrative Physiology, University of Colorado, Boulder, Boulder, Colorado., Cuevas LM; Department of Integrative Physiology, University of Colorado, Boulder, Boulder, Colorado., Eng JS; Department of Integrative Physiology, University of Colorado, Boulder, Boulder, Colorado., Murphy MP; MRC Mitochondrial Biology Unit, University of Cambridge , Cambridge , United Kingdom., Seals DR; Department of Integrative Physiology, University of Colorado, Boulder, Boulder, Colorado. |
Jazyk: |
angličtina |
Zdroj: |
Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol (1985)] 2018 May 01; Vol. 124 (5), pp. 1194-1202. Date of Electronic Publication: 2017 Oct 26. |
DOI: |
10.1152/japplphysiol.00670.2017 |
Abstrakt: |
Aortic stiffening is a major independent risk factor for cardiovascular diseases, cognitive dysfunction, and other chronic disorders of aging. Mitochondria-derived reactive oxygen species are a key source of arterial oxidative stress, which may contribute to arterial stiffening by promoting adverse structural changes-including collagen overabundance and elastin degradation-and enhancing inflammation, but the potential for mitochondria-targeted therapeutic strategies to ameliorate aortic stiffening with primary aging is unknown. We assessed aortic stiffness [pulse-wave velocity (aPWV)], ex vivo aortic intrinsic mechanical properties [elastic modulus (EM) of collagen and elastin regions], and aortic protein expression in young (~6 mo) and old (~27 mo) male C57BL/6 mice consuming normal drinking water (YC and OC) or water containing mitochondria-targeted antioxidant MitoQ (250 µM; YMQ and OMQ) for 4 wk. Both baseline and postintervention aPWV values were higher in OC vs. YC (post: 482 ± 21 vs. 420 ± 5 cm/s, P < 0.05). MitoQ had no effect in young mice but decreased aPWV in old mice (OMQ, 426 ± 20, P < 0.05 vs. OC). MitoQ did not affect age-associated increases in aortic collagen-region EM, collagen expression, or proinflammatory cytokine expression, but partially attenuated age-associated decreases in elastin region EM and elastin expression. Our results demonstrate that MitoQ reverses in vivo aortic stiffness in old mice and suggest that mitochondria-targeted antioxidants may represent a novel, promising therapeutic strategy for decreasing aortic stiffness with primary aging and, possibly, age-related clinical disorders in humans. The destiffening effects of MitoQ treatment may be at least partially mediated by attenuation/reversal of age-related aortic elastin degradation. NEW & NOTEWORTHY We show that 4 wk of treatment with the mitochondria-specific antioxidant MitoQ in mice completely reverses the age-associated elevation in aortic stiffness, assessed as aortic pulse-wave velocity. The destiffening effects of MitoQ treatment may be at least partially mediated by attenuation of age-related aortic elastin degradation. Our results suggest that mitochondria-targeted therapeutic strategies may hold promise for decreasing arterial stiffening with aging in humans, possibly decreasing the risk of many chronic age-related clinical disorders. |
Databáze: |
MEDLINE |
Externí odkaz: |
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