Key result
Periprocedural myocardial injury is linked to ~68% higher PBMC caspase-1 activity, reflecting NLRP3 activation.
Why the study?
Periprocedural myocardial injury is a common complication of PCI linked to poor prognosis, and while inflammation plays a crucial role, how it is initiated or sustained remains elusive.
Is NLRP3 inflammasome activation associated with periprocedural myocardial injury in patients undergoing elective PCI?
Cohort (n=65)
Single-blind
No
Is NLRP3 inflammasome activation associated with periprocedural myocardial injury in patients undergoing elective PCI?
NLRP3 inflammasome activation is significantly associated with periprocedural myocardial injury during elective PCI, suggesting a possible therapeutic target.
NLRP3 inflammasome assessment should not yet guide periprocedural care in elective PCI; hypothesis-generating for targeted inhibition trials.
BackgroundPeriprocedural 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.MethodsRNA-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.ResultsWe 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.ConclusionsWe discovered that NLRP3 inflammasome was involved in PMI, thus providing evidence supporting the therapeutic value of NLRP3 inflammasome-targeted strategies in PMI.
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Chen et al. (2023) conducted a cohort in Stable coronary artery disease (n=65). Periprocedural myocardial injury (PMI) vs. Non-PMI was evaluated on Caspase-1 activity in PBMCs (p=<0.01). Periprocedural myocardial injury was associated with significantly increased caspase-1 activity in PBMCs compared to non-PMI, indicating NLRP3 inflammasome activation.
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