Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, PR China.
Clin Chem Lab Med. 2013 Jul;51(7):1521-8. doi: 10.1515/cclm-2012-0600.
The nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome is a multiprotein complex consisting of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1. In peripheral blood mononuclear cells (PBMCs), NLRP3 can activate interleukin-1β (IL-1β), important in the chronic inflammatory process of idiopathic dilated cardiomyopathy (IDCM). Therefore, the NLRP3 inflammasome in PBMCs may be involved in the pathogenesis of IDCM. We evaluated the association of circulating levels of NLRP3 inflammasome and cardiac function in patients with IDCM and 6-month rehospitalization.
We enrolled 54 patients with IDCM and 20 healthy volunteers and analyzed left ventricle ejection fraction (LVEF), electrocardiography findings and circulating levels of NLRP3, ASC, caspase-1, IL-1β, N terminal-pro type B natriuretic peptide (NT-pro BNP) and blood values. Patients were followed up for 6 months.
On admission and discharge, the circulating levels of NLRP3, ASC, caspase-1 and IL-1β were higher in IDCM patients than healthy controls (all p<0.05). In patients, NLRP3 mRNA level was associated with LVEF, NT-pro BNP level and monocyte count (all p<0.05). LVEF at admission and mRNA levels of NLRP3 and IL-1β at discharge were independent risk factors of 6-month rehospitalization for patients. High NLRP3 mRNA level was associated with cumulative rehospitalization rate (p<0.05).
NLRP3 level in PBMCs may be associated with cardiac function and rehospitalization in IDCM patients.
核苷酸结合寡聚化结构域样受体 3(NLRP3)炎性小体是一种多蛋白复合物,由 NLRP3、含有半胱氨酸天冬氨酸蛋白酶募集结构域(ASC)的凋亡相关斑点样蛋白和半胱氨酸天冬氨酸蛋白酶-1 组成。在外周血单核细胞(PBMCs)中,NLRP3 可以激活白细胞介素-1β(IL-1β),这在特发性扩张型心肌病(IDCM)的慢性炎症过程中非常重要。因此,PBMCs 中的 NLRP3 炎性小体可能参与 IDCM 的发病机制。我们评估了 IDCM 患者外周血 NLRP3 炎性小体与心脏功能和 6 个月再入院的关系。
我们纳入了 54 例 IDCM 患者和 20 名健康志愿者,并分析了左心室射血分数(LVEF)、心电图结果以及 NLRP3、ASC、半胱氨酸天冬氨酸蛋白酶-1、IL-1β、N 末端-pro 型 B 利钠肽(NT-pro BNP)和血液值的循环水平。患者进行了 6 个月的随访。
入院和出院时,IDCM 患者的 NLRP3、ASC、半胱氨酸天冬氨酸蛋白酶-1 和 IL-1β 的循环水平均高于健康对照组(均 p<0.05)。在患者中,NLRP3 mRNA 水平与 LVEF、NT-pro BNP 水平和单核细胞计数相关(均 p<0.05)。入院时的 LVEF 和出院时的 NLRP3 和 IL-1βmRNA 水平是患者 6 个月再入院的独立危险因素。高 NLRP3 mRNA 水平与累积再入院率相关(p<0.05)。
PBMCs 中的 NLRP3 水平可能与 IDCM 患者的心脏功能和再入院相关。