Vulesevic Branka, Lavoie Simon S, Neagoe Paul-Eduard, Dumas Elizabeth, Räkel Agnès, White Michel, Sirois Martin G
Centre de Recherche, Institut de Cardiologie de Montréal, Faculté de Médecine, Université de Montréal, Montreal, Quebec H1T 1C8, Canada.
Département de Pharmacologie et Physiologie, Faculté de Médecine, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.
Immunohorizons. 2019 Aug 9;3(8):378-388. doi: 10.4049/immunohorizons.1900026.
C-reactive protein (CRP) is recognized as a biomarker of chronic, low-grade inflammation associated with vascular disorders. Lately, the role of neutrophils and neutrophil extracellular traps (NETs) has been investigated as a potential source of chronic inflammation and cardiovascular complications. This study investigated NETs as a marker of inflammation in patients with symptomatic heart failure (HF) with or without type 2 diabetes (T2DM) and examined the correlation between NETs and CRP. We performed a noninterventional study including patients with HF with or without T2DM, T2DM, and a healthy control (HC) group. NETs and other inflammatory markers in serum were measured by ELISA. The release of NETs (NETosis) in vitro under various stimuli was measured by confocal microscopy. The levels of NETs in the serum of HF patients were significantly higher compared with HC (112%). Serum CRP concentrations were significantly increased in HF and HF plus T2DM patients compared with HC, and a positive correlation was observed between serum CRP and NETs levels. Neutrophils from HF and HF plus T2DM patients underwent in vitro NETs release faster than T2DM and HC without any stimuli. In vitro, serum collected from the HF and the HF plus T2DM group induced NETosis in healthy neutrophils significantly more when compared with HC and T2DM, which was prevented by depletion from CRP. We confirmed in vitro that CRP induces a concentration-dependent NETs synthesis. This study proposes a mechanism by which CRP increases the risk of future cardiovascular events and supports mounting evidences on the role of neutrophils in chronic low-grade inflammation associated with HF.
C反应蛋白（CRP）被认为是与血管疾病相关的慢性低度炎症的生物标志物。最近，中性粒细胞和中性粒细胞胞外陷阱（NETs）的作用已被作为慢性炎症和心血管并发症的潜在来源进行研究。本研究调查了NETs作为有或无2型糖尿病（T2DM）的症状性心力衰竭（HF）患者炎症标志物的情况，并检测了NETs与CRP之间的相关性。我们进行了一项非干预性研究，纳入了有或无T2DM的HF患者、T2DM患者以及健康对照组（HC）。通过酶联免疫吸附测定法（ELISA）检测血清中的NETs和其他炎症标志物。通过共聚焦显微镜测量各种刺激下体外NETs的释放（NETosis）。与HC相比，HF患者血清中的NETs水平显著更高（高出112%）。与HC相比，HF患者和HF合并T2DM患者的血清CRP浓度显著升高，并且观察到血清CRP与NETs水平之间呈正相关。来自HF患者和HF合并T2DM患者的中性粒细胞在无任何刺激的情况下比T2DM患者和HC患者的中性粒细胞在体外更快地释放NETs。在体外，与HC和T2DM组相比，从HF组和HF合并T2DM组收集的血清在健康中性粒细胞中诱导NETosis的作用显著更强，而CRP的消耗可阻止这种作用。我们在体外证实CRP可诱导浓度依赖性的NETs合成。本研究提出了一种机制，通过该机制CRP增加了未来心血管事件的风险，并支持了关于中性粒细胞在与HF相关的慢性低度炎症中作用的越来越多的证据。
