Association of oxidative DNA damage and C-reactive protein in women at risk for cardiovascular disease.

Association of oxidative DNA damage and C-reactive protein in women at risk for cardiovascular disease.
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DOI:
10.1161/atvbaha.112.300276
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发表时间:
2012-11
期刊:
Arteriosclerosis, thrombosis, and vascular biology
影响因子:
--
通讯作者:
Evans MK
Evans MK
中科院分区:
其他
文献类型:
--
作者:
Noren Hooten N;Ejiogu N;Zonderman AB;Evans MK

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本研究的目的是在来自HANDLS研究(一项纵向流行病学研究)的中年妇女中,检查炎症临床标志物与8-氧代-7,8-二氢-2 ′脱氧鸟苷(8-oxodG)(一种氧化应激标志物)之间的关系。我们检查了一组年龄和种族匹配的女性中常见的炎症标志物DNA碱基加合物8-oxodG,这是一种氧化应激和心血管危险因素的标志物,分为三组(每组n=39),hsCRP低(<3 mg/L),中(>3-20 mg/L)和高(>20 mg/L)。我们发现hsCRP水平与氧化应激标志物8-oxodG之间存在显著相关性。8-oxodG与收缩压、脉压、IL-23呈正相关。hsCRP与肥胖变量、HDL、血清胰岛素水平、IL-12 p70和ICAM-1相关。原代人内皮细胞与hsCRP的孵育在体外产生活性氧。此外,hsCRP特异性诱导DNA碱基损伤,但不诱导其他形式的DNA损伤,包括单链和双链断裂。这些数据表明,在女性中,8-oxodG与hsCRP相关,并与选择的心血管危险因素独立相关。我们在女性中的数据表明,hsCRP可能通过增加氧化应激而导致心血管疾病。
The aim of the current study was to examine the relationship between clinical markers of inflammation and 8-oxo-7,8-dihydro-2′deoxyguanosine (8-oxodG), an oxidative stress marker, in middle-aged women drawn from the HANDLS study, a longitudinal epidemiologic study. We examined commonly assayed markers of inflammation, the DNA base adduct 8-oxodG, a marker of oxidative stress and cardiovascular risk factors in a cohort of women matched on age and race in three groups (n=39 per group) who had low (<3 mg/L) hsCRP, mid (>3–20 mg/L), and high (>20 mg/L) hsCRP. We found a significant relationship between hsCRP level and the oxidative stress marker, 8-oxodG. 8-oxodG was positively correlated with systolic blood pressure, pulse pressure and IL-23. hsCRP was associated with obesity variables, HDL, serum insulin levels, IL-12p70 and ICAM-1. Incubation of primary human endothelial cells with hsCRP generated reactive oxygen species in vitro. Furthermore, hsCRP specifically induced DNA base lesions, but not other forms of DNA damage including single and double strand breaks. These data suggest that in women 8-oxodG is associated with hsCRP and is independently related to select cardiovascular risk factors. Our data in women suggest that hsCRP may contribute to cardiovascular disease by increasing oxidative stress.