Pedicino Daniela, Severino Anna, Ucci Sara, Bugli Francesca, Flego Davide, Giglio Ada F, Trotta Francesco, Ruggio Aureliano, Lucci Claudia, Iaconelli Antonio, Paroni Sterbini Francesco, Biasucci Luigi M, Sanguinetti Maurizio, Glieca Franco, Luciani Nicola, Massetti Massimo, Crea Filippo, Liuzzo Giovanna
Institute of Cardiology, Catholic University, Rome, Italy.
Microbiology, Catholic University, Rome, Italy.
Int J Cardiol. 2017 Jun 1;236:95-99. doi: 10.1016/j.ijcard.2017.02.040. Epub 2017 Feb 16.
Epicardial adipose tissue (EAT) has a close functional and anatomic relationship with epicardial coronary arteries. Accumulating evidence suggests that host microbiome alterations may play a role in several inflammatory/immune disorders, triggering a robust proinflammatory response also involving interleukin-1β (IL-1β) and the NALP3 inflammasome. In the current study, we explore the hypothesis that in patients with non-ST elevation acute coronary syndrome (ACS), EAT contains potentially pro-atherosclerotic bacteria that might elicit inflammasome activation.
EAT samples were obtained during coronary artery bypass grafting from ACS (n=18) and effort stable angina (SA; n=16) patients, and as controls, from patients with angiographically normal coronary arteries undergoing surgery for mitral insufficiency (MVD; n=13). In all patients, NALP3 and proIL-1β mRNA expressions were evaluated with qRT-PCR. In 3 patients from each group, EAT microbiota composition was determined using next-generation sequencing technologies.
In EAT, mRNA expression of both NALP3 and pro-IL1β was significantly higher in ACS than in SA and MVD (P=0.028 and P=0.005, respectively). A broad range of bacterial species (n=76) was identified in both ACS and SA, with different predominant species. In contrast, microbial DNA was barely observed in MVD.
Our study demonstrated the presence of bacterial DNA directly into EAT, surrounding diseased coronary arteries, of patients with ACS. Furthermore, ACS is associated with NALP3/inflammasome pathway activation in EAT. Our data suggest that the EAT environment is susceptible to microbial colonization that might stimulate a proinflammatory response. These findings add new elements to the pathogenesis of ACS and suggest novel therapeutic targets.
心外膜脂肪组织（EAT）与心外膜冠状动脉存在密切的功能和解剖关系。越来越多的证据表明，宿主微生物群的改变可能在多种炎症/免疫疾病中起作用，引发强烈的促炎反应，其中也涉及白细胞介素-1β（IL-1β）和NALP3炎性小体。在本研究中，我们探讨了以下假设：在非ST段抬高型急性冠状动脉综合征（ACS）患者中，EAT含有可能引发炎性小体激活的潜在促动脉粥样硬化细菌。
在冠状动脉旁路移植术中从ACS患者（n = 18）和劳力性稳定型心绞痛（SA；n = 16）患者获取EAT样本，并作为对照，从接受二尖瓣关闭不全手术（MVD；n = 13）且冠状动脉造影正常的患者获取样本。对所有患者，采用qRT-PCR评估NALP3和proIL-1β mRNA表达。每组选取3例患者使用下一代测序技术测定EAT微生物群组成。
在EAT中，ACS患者的NALP3和pro-IL1β mRNA表达均显著高于SA患者和MVD患者（分别为P = 0.028和P = 0.005）。在ACS和SA患者中均鉴定出广泛的细菌种类（n = 76），优势菌种不同。相比之下，在MVD患者中几乎未观察到微生物DNA。
我们的研究证明了ACS患者病变冠状动脉周围的EAT中存在细菌DNA。此外，ACS与EAT中NALP3/炎性小体途径激活相关。我们的数据表明，EAT环境易受微生物定植影响，这可能刺激促炎反应。这些发现为ACS的发病机制增添了新元素，并提示了新的治疗靶点。
