Kinzenbaw Dale A, Chu Yi, Peña Silva Ricardo A, Didion Sean P, Faraci Frank M
Department of Internal Medicine, Cardiovascular Center, Carver College of Medicine, University of Iowa Iowa City, 52242, Iowa.
Department of Internal Medicine, Cardiovascular Center, Carver College of Medicine, University of Iowa Iowa City, 52242, Iowa ; Department of Pharmacology, University of Mississippi Medical Center Jackson, 39216, Mississippi.
Physiol Rep. 2013 Nov;1(6):e00149. doi: 10.1002/phy2.149. Epub 2013 Nov 11.
Carotid and cerebrovascular disease increase markedly with age contributing to stroke and cognitive impairment. Inflammation is a key element of vascular disease. In these studies, we tested the hypothesis that interleukin-10 (IL-10), a potent anti-inflammatory cytokine, protects against aging-induced endothelial dysfunction. Responses of carotid arteries from adult (5 ± 1 months) and old (22 ± 1 months) wild-type and IL-10-deficient mice were examined in vitro. Acetylcholine (an endothelium-dependent agonist) produced relaxation in arteries from adult wild-type that was not altered in old mice. In contrast, relaxation to acetylcholine in arteries from old IL-10-deficient mice was reduced by ∼50% (P < 0.05). Tempol, a scavenger of superoxide, did not affect responses in adult or old wild-type mice, but restored vasodilation to acetylcholine to normal in old IL-10-deficient mice. Responses of the carotid artery to nitroprusside (an endothelium-independent agonist) were not altered in any group. Vascular expression of IL-6 (a proinflammatory mediator of vascular disease) and components of NADPH oxidase (a major source of superoxide) was increased in old IL-10-deficient mice compared with wild-type (P < 0.05). These findings provide the first evidence that age-related and superoxide-mediated endothelial dysfunction occurs earlier with IL-10 deficiency. Our findings suggest a novel role for IL-10 to protect against age-related increases in expression of IL-6, oxidative stress, and endothelial dysfunction.
颈动脉和脑血管疾病随年龄增长显著增加，会导致中风和认知障碍。炎症是血管疾病的关键因素。在这些研究中，我们验证了白细胞介素 - 10（IL - 10）这一强效抗炎细胞因子可预防衰老诱导的内皮功能障碍的假说。在体外检测了成年（5±1个月）和老年（22±1个月）野生型及IL - 10基因缺陷小鼠的颈动脉反应。乙酰胆碱（一种内皮依赖性激动剂）可使成年野生型小鼠的动脉舒张，老年小鼠的这一反应未改变。相比之下，老年IL - 10基因缺陷小鼠动脉对乙酰胆碱的舒张反应降低了约50%（P < 0.05）。超氧化物清除剂Tempol对成年或老年野生型小鼠的反应无影响，但可使老年IL - 10基因缺陷小鼠对乙酰胆碱的血管舒张恢复正常。任何组中颈动脉对硝普钠（一种内皮非依赖性激动剂）的反应均未改变。与野生型相比，老年IL - 10基因缺陷小鼠中血管疾病促炎介质IL - 6及NADPH氧化酶（超氧化物的主要来源）成分的血管表达增加（P < 0.05）。这些发现首次证明，IL - 10缺乏会使与年龄相关的、超氧化物介导的内皮功能障碍更早出现。我们的研究结果表明IL - 10在预防与年龄相关的IL - 6表达增加、氧化应激和内皮功能障碍方面具有新作用。
