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糖尿病与衰老诱导的血管炎症

Diabetes and ageing-induced vascular inflammation.

作者信息

Assar Mariam El, Angulo Javier, Rodríguez-Mañas Leocadio

机构信息

Instituto de Investigación Sanitaria del Hospital Universitario de Getafe, Getafe, Spain.

Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, Madrid, Spain.

出版信息

J Physiol. 2016 Apr 15;594(8):2125-46. doi: 10.1113/JP270841. Epub 2015 Nov 2.

Abstract

Diabetes and the ageing process independently increase the risk for cardiovascular disease (CVD). Since incidence of diabetes increases as people get older, the diabetic older adults represent the largest population of diabetic subjects. This group of patients would potentially be threatened by the development of CVD related to both ageing and diabetes. The relationship between CVD, ageing and diabetes is explained by the negative impact of these conditions on vascular function. Functional and clinical evidence supports the role of vascular inflammation induced by the ageing process and by diabetes in vascular impairment and CVD. Inflammatory mechanisms in both aged and diabetic vasculature include pro-inflammatory cytokines, vascular hyperactivation of nuclear factor-кB, increased expression of cyclooxygenase and inducible nitric oxide synthase, imbalanced expression of pro/anti-inflammatory microRNAs, and dysfunctional stress-response systems (sirtuins, Nrf2). In contrast, there are scarce data regarding the interaction of these mechanisms when ageing and diabetes co-exist and its impact on vascular function. Older diabetic animals and humans display higher vascular impairment and CVD risk than those either aged or diabetic, suggesting that chronic low-grade inflammation in ageing creates a vascular environment favouring the mechanisms of vascular damage driven by diabetes. Further research is needed to determine the specific inflammatory mechanisms responsible for exacerbated vascular impairment in older diabetic subjects in order to design effective therapeutic interventions to minimize the impact of vascular inflammation. This would help to prevent or delay CVD and the specific clinical manifestations (cognitive decline, frailty and disability) promoted by diabetes-induced vascular impairment in the elderly.

摘要

糖尿病和衰老过程会独立增加心血管疾病(CVD)的风险。由于糖尿病的发病率随着人们年龄的增长而增加,老年糖尿病患者是糖尿病患者中人数最多的群体。这群患者可能会受到与衰老和糖尿病相关的心血管疾病发展的威胁。心血管疾病、衰老和糖尿病之间的关系可以通过这些状况对血管功能的负面影响来解释。功能和临床证据支持衰老过程和糖尿病诱导的血管炎症在血管损伤和心血管疾病中的作用。老年和糖尿病血管中的炎症机制包括促炎细胞因子、核因子-κB的血管过度活化、环氧化酶和诱导型一氧化氮合酶表达增加、促炎/抗炎微小RNA表达失衡以及应激反应系统(沉默调节蛋白、核因子E2相关因子2)功能失调。相比之下,关于衰老和糖尿病共存时这些机制的相互作用及其对血管功能的影响的数据却很少。老年糖尿病动物和人类比单纯衰老或糖尿病的动物和人类表现出更高的血管损伤和心血管疾病风险,这表明衰老过程中的慢性低度炎症会营造一种血管环境,有利于糖尿病驱动的血管损伤机制。需要进一步研究以确定导致老年糖尿病患者血管损伤加剧的具体炎症机制,从而设计有效的治疗干预措施,以尽量减少血管炎症的影响。这将有助于预防或延缓心血管疾病以及老年糖尿病诱导的血管损伤所引发的特定临床表现(认知衰退、虚弱和残疾)。

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