Silveira Angela, McLeod Olga, Strawbridge Rona J, Gertow Karl, Sennblad Bengt, Baldassarre Damiano, Veglia Fabrizio, Deleskog Anna, Persson Jonas, Leander Karin, Gigante Bruna, Kauhanen Jussi, Rauramaa Rainer, Smit Andries J, Mannarino Elmo, Giral Philippe, Gustafsson Sven, Söderberg Stefan, Öhrvik John, Humphries Steve E, Tremoli Elena, de Faire Ulf, Hamsten Anders
Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Atherosclerosis. 2015 Mar;239(1):125-30. doi: 10.1016/j.atherosclerosis.2014.12.046. Epub 2014 Dec 23.
Genetic variants robustly associated with coronary artery disease were reported in the vicinity of the interleukin (IL)-5 locus, and animal studies suggested a protective role for IL-5 in atherosclerosis. Therefore, we set this work to explore IL-5 as a plasma biomarker for early subclinical atherosclerosis, as determined by measures of baseline severity and change over time of carotid intima-media thickness (cIMT).
We used biobank and databases of IMPROVE, a large European prospective cohort study of high-risk individuals (n = 3534) free of clinically overt cardiovascular disease at enrollment, in whom composite and segment-specific measures of cIMT were recorded at baseline and after 15 and 30 months. IL-5 was measured with an immunoassay in plasma samples taken at baseline.
IL-5 levels were lower in women than in men, lower in the South than in North of Europe, and showed positive correlations with most established risk factors. IL-5 showed significant inverse relationships with cIMT change over time in the common carotid segment in women, but no significant relationships to baseline cIMT in either men or women.
Our results suggest that IL-5 may be part of protective mechanisms operating in early atherosclerosis, at least in women. However, the relationships are weak and whereas IL-5 has been proposed as a potential molecular target to treat allergies, it is difficult to envisage such a scenario in coronary artery disease.
在白细胞介素（IL）-5基因座附近报道了与冠状动脉疾病密切相关的基因变异，动物研究表明IL-5在动脉粥样硬化中具有保护作用。因此，我们开展此项研究，以探索IL-5作为早期亚临床动脉粥样硬化的血浆生物标志物，通过颈动脉内膜中层厚度（cIMT）的基线严重程度和随时间变化的测量来确定。
我们使用了IMPROVE生物样本库和数据库，这是一项针对高危个体的大型欧洲前瞻性队列研究（n = 3534），入组时无临床明显心血管疾病，在基线、15个月和30个月时记录了cIMT的综合和节段特异性测量值。在基线时采集的血浆样本中用免疫测定法测量IL-5。
女性的IL-5水平低于男性，欧洲南部低于北部，并且与大多数已确定的危险因素呈正相关。在女性中，IL-5与颈总动脉节段cIMT随时间的变化呈显著负相关，但在男性或女性中与基线cIMT均无显著关系。
我们的结果表明，IL-5可能是早期动脉粥样硬化中起作用的保护机制的一部分，至少在女性中是这样。然而，这种关系较弱，虽然IL-5已被提议作为治疗过敏的潜在分子靶点，但在冠状动脉疾病中很难设想这样的情况。
