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人类动脉粥样硬化趋化因子/细胞因子标志物性别差异的初步研究。

Pilot study of sex differences in chemokine/cytokine markers of atherosclerosis in humans.

作者信息

Leung Joseph, Jayachandran Muthuvel, Kendall-Thomas June, Behrenbeck Thomas, Araoz Philip, Miller Virginia M

机构信息

Department of Surgery, Physiology, and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

出版信息

Gend Med. 2008 Mar;5(1):44-52. doi: 10.1016/s1550-8579(08)80007-1.

DOI:10.1016/s1550-8579(08)80007-1
PMID:18420165
Abstract

BACKGROUND

Atherogenic processes increase in women after menopause, when the risk of cardiovascular adverse events approaches that observed in age-matched men. In experimental animals, ovariectomy increases the platelet content of mitogenic cytokines, such as platelet-derived growth factor (PDGF), which when released into the blood or site of vascular injury, contribute to atherogenic processes.

OBJECTIVE

Experiments were designed to assess the sex distribution of inflammatorychemokines/cytokines, which may be released from platelets in the serum of middle-aged women and men in whom the extent of atherosclerotic coronary disease was defined by coronary arterial calcification (CAC).

METHODS

Blood was obtained from healthy white individuals recruited from the Mayo Clinic database. CAC was assessed by 64-slice computed tomography. Plasma cholesterol, lipids, and high-sensitivity C-reactive protein were analyzed by the Mayo Clinic Department of Laboratory Medicine and Pathology. Serum cytokines were determined using cytokine arrays. Cytokine expression was measured using dot blot analysis.

RESULTS

Of the 16 individuals (11 women, 5 men) who agreed to participate in the study, 1 woman was premenopausal, 1 was taking oral contraceptives, and 1 was receiving menopausal hormone therapy. One woman had an active infection and was eliminated from the study. CAC was detected in only 2 of the 11 women (scores of 46 and 56 Agatston units [AU]) but in 3 of the 5 men (scores of 3, 123, and 609 AU). Correcting for all other risk factors, expression of the chemokine RANTES (regulated on activation, normal, T-cell expressed and secreted; CCL5 [CC chemokine ligand 5]) was 100.98% greater in women than in men, and PDGF-BB was 55.30% greater in women than in men.

CONCLUSIONS

This small pilot study found that the circulating chemokines/cytokines RANTES and PDGF-BB showed sex-disparate distribution between the women and men studied, and did not appear related to the degree of CAC.

摘要

背景

绝经后女性的致动脉粥样硬化过程会增加,此时心血管不良事件的风险接近年龄匹配男性的水平。在实验动物中,卵巢切除术会增加有丝分裂细胞因子的血小板含量,如血小板衍生生长因子(PDGF),当这些因子释放到血液或血管损伤部位时,会促进致动脉粥样硬化过程。

目的

设计实验以评估炎症趋化因子/细胞因子的性别分布,这些因子可能从患有冠状动脉钙化(CAC)的中年女性和男性血清中的血小板释放出来。

方法

从梅奥诊所数据库招募的健康白人个体中获取血液。通过64层计算机断层扫描评估CAC。梅奥诊所检验医学与病理学系分析血浆胆固醇、脂质和高敏C反应蛋白。使用细胞因子阵列测定血清细胞因子。使用斑点印迹分析测量细胞因子表达。

结果

在同意参与研究的16名个体(11名女性,5名男性)中,1名女性处于绝经前,1名正在服用口服避孕药,1名正在接受绝经激素治疗。1名女性有活动性感染,被排除在研究之外。11名女性中仅2名检测到CAC(阿加斯顿单位[AU]评分分别为46和56),但5名男性中有3名检测到(评分分别为3、123和609 AU)。校正所有其他危险因素后,趋化因子RANTES(活化调节、正常、T细胞表达和分泌;CCL5[CC趋化因子配体5])在女性中的表达比男性高100.98%,PDGF-BB在女性中的表达比男性高55.30%。

结论

这项小型初步研究发现,循环趋化因子/细胞因子RANTES和PDGF-BB在研究的女性和男性之间表现出性别差异分布,且似乎与CAC程度无关。

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