Beibei Luo1, Fan Wang, Bo Li, Zhe Dong, Xiaoman Liu, Cheng Zhang, Fengshuang An. 1. 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.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: NLRP3 level in PBMCs may be associated with cardiac function and rehospitalization in IDCM patients.
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS:NLRP3 level in PBMCs may be associated with cardiac function and rehospitalization in IDCM patients.
Authors: Stefano Toldo; Eleonora Mezzaroma; Leo F Buckley; Nicola Potere; Marcello Di Nisio; Giuseppe Biondi-Zoccai; Benjamin W Van Tassell; Antonio Abbate Journal: Pharmacol Ther Date: 2021-12-11 Impact factor: 13.400