Mitochondria-targeted antioxidant therapy with MitoQ ameliorates aortic stiffening in old mice

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 weeks. Both baseline and post-intervention aPWV values were higher in OC versus YC (post: 482 ± 21 vs. 420 ± 5 cm/sec, p<0.05). MitoQ had no effect in young mice but reduced 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 pro-inflammatory cytokine expression, but partially attenuated age-associated decreases in elastin-region EM and elastin expression. Our results demonstrating that MitoQ reverses in vivo aortic stiffness in old mice suggest that mitochondria-targeted antioxidants may represent a novel, promising therapeutic strategy for reducing aortic stiffness with primary aging and, possibly, age-related clinical disorders in humans. The de-stiffening effects of MitoQ treatment may be at least partially mediated by attenuation/reversal of age-related aortic elastin degradation.

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