Unique monocyte transcriptomic profiles are associated with preclinical atherosclerosis in women with systemic lupus erythematosus (SLE)
Unique monocyte transcriptomic profiles are associated with preclinical atherosclerosis in women with systemic lupus erythematosus (SLE)
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DOI：
10.1101/2020.08.05.20169136
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发表时间：
2020-08
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影响因子：
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通讯作者：
L. Woodridge;E. Chocano;P. Ashford;G. Robinson;K. Waddington;Anisur Rahman;C. Orengo;E. Jury;I. Torra
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文献类型：
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作者：
L. Woodridge;E. Chocano;P. Ashford;G. Robinson;K. Waddington;Anisur Rahman;C. Orengo;E. Jury;I. Torra
与一般人群相比，患有系统性红斑狼疮 (SLE) 的女性心血管风险显着增加。然而，尽管心血管疾病是这些女性发病和死亡的主要原因，但这种增加的风险并未在临床上得到管理，并且缺乏剖析和预测其心血管风险的工具。值得注意的是，这种升高的 CVD 风险并没有被传统的风险因素所捕获。为了探索 SLE 无症状动脉粥样硬化的分子程序，我们使用了一组特征明确的无 CVD 的 SLE 女性，使用颈动脉和股动脉的非侵入性超声成像扫描无症状的动脉粥样硬化斑块。我们研究了患有或不患有临床前动脉粥样硬化的 SLE 女性 CD14+ 循环单核细胞的转录组学特征。我们确定了独特的单核细胞基因表达谱，可以区分 SLE 女性临床前斑块的存在。此外，先进的生物信息学分析揭示了所识别基因之间的功能途径和相互作用，可以解释斑块形成的机制差异。我们认为这些分子特征可以帮助理解为什么一部分患有系统性红斑狼疮的女性容易患上动脉粥样硬化，并且患上临床心血管疾病的风险更高。与其他努力一起，这些分子见解将有助于更好地定义 SLE 背景下的动脉粥样硬化，这对于未来的患者分层和抗动脉粥样硬化疗法的识别至关重要。
Women with Systemic Lupus Erythematosus (SLE) show significantly increased cardiovascular risk compared to the general population. However, despite CVD being a major cause of morbidity and mortality for these women, this increased risk is not managed clinically and tools to dissect and predict their cardiovascular risk are lacking. Notably, this elevated CVD risk is not captured by traditional risk factors. To explore molecular programs underlying asymptomatic atherosclerosis in SLE we used a well-characterised cohort of CVD-free women with SLE, scanned for asymptomatic atherosclerotic plaques using non-invasive ultrasound imaging of the carotid and femoral arteries. We investigated the transcriptomic profiles of CD14+ circulating monocytes in women with SLE with or without preclinical atherosclerosis. We identified unique monocytic gene expression profiles that distinguished the presence of preclinical plaques in women with SLE. In addition, advanced bioinformatic analysis revealed functional pathways and interactions between the genes identified that could explain mechanistic differences in plaque formation. We propose that these molecular signatures could help understand why a subset of women with SLE are predisposed to develop atherosclerosis and at higher risk of developing clinical CVD. Collectively with other efforts, these molecular insights will help to better define atherosclerosis in the context of SLE which will be critical for future patient stratification and identification of anti-atherosclerotic therapies.