Association between NLRP3 inflammasome and periprocedural myocardial injury following elective PCI
Ao Chen,
Danbo Lu,
Zheng Yang,
Xinyu Che,
Yan Xia,
Xia Shao,
Zhangwei Chen,
Juying Qian,
Junbo Ge
Affiliations
Ao Chen
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai, China; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, China
Danbo Lu
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai, China; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, China
Zheng Yang
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
Xinyu Che
Shanghai Institute of Infectious Disease and Biosecurity, Zhongshan Hospital, Fudan University, Shanghai, China
Yan Xia
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai, China; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, China
Xia Shao
Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China
Zhangwei Chen
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai, China; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, China; Corresponding author. Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China.
Juying Qian
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai, China; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, China; Corresponding author. Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Junbo Ge
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai, China; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, China
Background: Periprocedural myocardial injury (PMI) is a common complication of percutaneous coronary intervention (PCI) associated with poor prognosis. Inflammation has been demonstrated to exert a crucial role in PMI. However, how the inflammation is initiated or sustained in PMI remains elusive. Methods: RNA-seq in peripheral blood mononuclear cells (PBMCs) from 3 Non-PMI and 6 PMI patients was performed with subsequent bioinformatics analysis. RNA-seq results were verified in a patient cohort. We also established the coronary microembolization (CME) mice model to mimic PMI. The activity of caspase-1 in PBMCs was detected by flow cytometry. The levels of interleukin (IL)-1β, IL-18 and cardiac troponin in plasma were measured by enzyme-linked immunosorbent assay. Results: We identified a total of 901 differentially expressed genes (DEGs) between Non-PMI and PMI patients. These DEGs participated in several inflammation-related processes. NOD-like receptor signaling pathway was significantly enriched in pathway analysis. All the key genes composed in the NLRP3 inflammasome, including NLRP3, PYCARD, CASP1 and IL1B, were upregulated in PMI patients. The activation of NLRP3 inflammasome was then verified by increased activity of caspase-1 in PBMCs, and elevated levels of IL-1β and IL-18 in plasma in PMI patients. Spearman analysis confirmed tight correlations between caspase-1 activity, IL-1β, IL-18 levels and troponin T level. In addition, caspase-1 activity, IL-1β and IL-18 levels were also enhanced in CME mice. Conclusions: We discovered that NLRP3 inflammasome was involved in PMI, thus providing evidence supporting the therapeutic value of NLRP3 inflammasome-targeted strategies in PMI.
