阿片肽浓度与类风湿性关节炎中动脉粥样硬化斑块稳定性介质水平的改变及动脉粥样硬化相关。
Apelin concentrations are associated with altered atherosclerotic plaque stability mediator levels and atherosclerosis in rheumatoid arthritis.
作者信息
Gunter Sule, Solomon Ahmed, Tsang Linda, Woodiwiss Angela J, Robinson Chanel, Millen Aletta M E, Norton Gavin R, Dessein Patrick H
机构信息
Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Department of Rheumatology, Charlotte Maxeke Johannesburg Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, South Africa.
出版信息
Atherosclerosis. 2017 Jan;256:75-81. doi: 10.1016/j.atherosclerosis.2016.11.024. Epub 2016 Nov 24.
BACKGROUND AND AIMS
Apelin-APJ signaling reduces cardiovascular disease (CVD) risk. In rheumatoid arthritis (RA), the atherosclerosis burden and plaque vulnerability to rupture are increased. We explored relationships between apelin concentrations and subclinical CVD in RA.
METHODS
Apelin levels were measured in 235 (114 black, 121 white) RA patients. Associations between apelin concentrations and ultrasound determined carotid artery intima-media thickness (cIMT) and plaque, and levels of matrix metalloproteinase (MMP)-2 and -9 that mediate plaque stability and vulnerability respectively, were identified in confounder adjusted multivariate regression analysis.
RESULTS
In all patients, apelin concentrations were directly associated with those of MMP-2 (β (SE) = 0.324 (0.112), p = 0.004) and inversely with those of MMP-9 (β (SE) = -0.239 (0.060), p = 0.000). Apelin concentration-subclinical CVD relations were influenced by population origin, RA disease activity, erythrocyte sedimentation rate (ESR) and interleukin (IL)-6 concentrations (interaction p = 0.001 to 0.04). Accordingly, the apelin-MMP-2 concentration relationship was reproduced in white (β (SE) = 0.367 (0.146), p = 0.01) but not black RA patients (β (SE) = 0.197 (0.220), p = 0.4), and only in those without (but not with) large erythrocyte sedimentation rates (β (SE) = 0.428 (0.143), p = 0.003) or interleukin-6 levels (β (SE) = 0.485 (0.288), p = 0.04). By contrast, the apelin-MMP-9 concentration relation was reproduced more consistently. Apelin levels were inversely related to cIMT in patients with RA remission or mild (β (SE) = -0.068 (0.033), p = 0.04) but not moderate or high disease activity (β (SE) = 0.015 (0.112), p = 0.7).
CONCLUSIONS
Apelin concentrations are associated with altered plaque stability mediator levels and atherosclerosis in patients with RA. These relations are partially dependent on population origin and systemic inflammatory status.
背景与目的
阿片肽-APJ信号通路可降低心血管疾病（CVD）风险。在类风湿关节炎（RA）中，动脉粥样硬化负担及斑块破裂易感性增加。我们探讨了RA患者中阿片肽浓度与亚临床CVD之间的关系。
方法
测定了235例（114例黑人、121例白人）RA患者的阿片肽水平。在进行了混杂因素校正的多变量回归分析中，确定了阿片肽浓度与超声测定的颈动脉内膜中层厚度（cIMT）和斑块，以及分别介导斑块稳定性和易损性的基质金属蛋白酶（MMP）-2和-9水平之间的关联。
结果
在所有患者中，阿片肽浓度与MMP-2浓度呈正相关（β（标准误）=0.324（0.112），p=0.004），与MMP-9浓度呈负相关（β（标准误）=-0.239（0.060），p=0.000）。阿片肽浓度与亚临床CVD的关系受人群来源、RA疾病活动度、红细胞沉降率（ESR）和白细胞介素（IL）-6浓度的影响（交互作用p=0.001至0.04）。因此，阿片肽与MMP-2浓度的关系在白人RA患者中重现（β（标准误）=0.367（0.146），p=0.01），但在黑人RA患者中未重现（β（标准误）=0.197（0.220），p=0.4），且仅在红细胞沉降率较低（而非较高）（β（标准误）=0.428（0.143），p=0.003）或白细胞介素-6水平较低（而非较高）（β（标准误）=0.485（0.288），p=0.04）的患者中重现。相比之下，阿片肽与MMP-9浓度的关系重现得更为一致。在病情缓解或轻度的RA患者中，阿片肽水平与cIMT呈负相关（β（标准误）=-0.068（0.033），p=0.04），但在中度或高度疾病活动度的患者中无此相关性（β（标准误）=0.015（0.112），p=0.7）。
结论
RA患者的阿片肽浓度与斑块稳定性介质水平改变及动脉粥样硬化有关。这些关系部分取决于人群来源和全身炎症状态。
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