The mitochondria‐targeted antioxidant improves age‐related cardiac damage

Senescence is a major factor to increase oxidant stressin mitochondria, which contributes to the pathogenesis of heart diseases. However, the effect of antioxidant therapy on cardiac mitochondria in aging related‐cardiac dysfunctionremains elusive. We postulated that scavenging superoxide targeted in mitochondriawould have benefit in the aged heart. Increased levels of superoxide and NADPH oxidase activity were appeared in old mice (62W) compared to those in young mice (8W) (Superoxide: 2.6±0.4 vs. 1.2±0.2 nmol/mg protein; NADPH oxidase activity: 2654±282 vs. 1124±156 RLU, P<0.01, n=12, respectively). In old mice treated with mitochondria‐targeted antioxidant MitoTEMPO coinfusion using minipump(180 µg/kg/day, 28 days), levels of superoxide and NADPH oxidase activity decreased (0.2±0.2 nmol/mg protein and 342±45 RLU, P<0.01). Echocardiography showed that treatment with MitoTEMPO in old mice improvedleft ventricular ejection fraction (from 48±5% to 62±5%, P<0.01) and diastolic dysfunction of theleft ventricle. Endothelium‐dependent vasodilation in isolated coronary arterioles and oxygen consumption rate in complex I and III of cardiac mitochondriawereimpaired in old mice compared to thosein young mice, which wereimprovedby MitoTEMPO treatment. Resolution of mitochondrial oxidantstress by MitoTEMPO in old mice restored cardiac function and coronary vasodilative capacity to the same magnitude observed in young mice. Therefore, antioxidant strategy targeting mitochondria could have therapeutic benefit in heart diseases with senescence.