Atherosclerosis · 2025
Basal and exercise-induced expression of NLRP3 inflammasome-related components is increased in patients with chronic coronary syndrome.
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Mahmood Zeid, Bäck Maria, Leanderson Per, Thune Rebecka, Skoglund Camilla, Jonasson Lena
Аннотация
BACKGROUND AND AIMS: NLRP3 inflammasome is considered a critical actor in the inflammatory process of coronary artery disease. Increased expression of NLRP3 inflammasome components has been reported in patients with acute coronary syndrome, but whether this persists beyond the acute phase is less known. We performed a prospective study to investigate whether basal and/or exercise-induced NLRP3 inflammasome components were elevated in patients with chronic coronary syndrome (CCS).
METHODS: Patients (n = 81) underwent exercise stress tests twice: 3-4 weeks and 3-6 months after a major coronary event, whereas controls (n = 30) performed it once. Concentrations of interleukin(IL)-18, IL-1Ra and IL-6 were measured before and 30 min after exercise. Genes related to NLRP3 inflammasome and NFκB signaling pathways were measured in blood mononuclear cells before and after exercise. On the first visit, patients were prescribed an exercise-based cardiac rehabilitation program. Physical activity levels were reported on both visits.
RESULTS: Patients were clinically stable and exhibited increased exercise capacity as well as increased self-reported physical activity between visits. Basal plasma levels of IL-18, as well as exercise-induced levels of IL-18 and IL-1Ra, were higher in patients compared with controls on both visits. Also, basal gene expression of NLRP3 was higher in patients, as were several NFκB-related genes. After exercise, gene expression related to NLRP3 inflammasome activation, in particular P2RX7, was higher in patients on both visits.
CONCLUSIONS: Up to 6 months after a coronary event, patients exhibited an increase in NLRP3 inflammasome-related components that was even more pronounced after acute exercise, compared with controls. The results indicate that a primed NLRP3 inflammasome system is maintained despite clinical stability and best available therapy, highlighting the need to further combat inflammation in patients with CCS.
METHODS: Patients (n = 81) underwent exercise stress tests twice: 3-4 weeks and 3-6 months after a major coronary event, whereas controls (n = 30) performed it once. Concentrations of interleukin(IL)-18, IL-1Ra and IL-6 were measured before and 30 min after exercise. Genes related to NLRP3 inflammasome and NFκB signaling pathways were measured in blood mononuclear cells before and after exercise. On the first visit, patients were prescribed an exercise-based cardiac rehabilitation program. Physical activity levels were reported on both visits.
RESULTS: Patients were clinically stable and exhibited increased exercise capacity as well as increased self-reported physical activity between visits. Basal plasma levels of IL-18, as well as exercise-induced levels of IL-18 and IL-1Ra, were higher in patients compared with controls on both visits. Also, basal gene expression of NLRP3 was higher in patients, as were several NFκB-related genes. After exercise, gene expression related to NLRP3 inflammasome activation, in particular P2RX7, was higher in patients on both visits.
CONCLUSIONS: Up to 6 months after a coronary event, patients exhibited an increase in NLRP3 inflammasome-related components that was even more pronounced after acute exercise, compared with controls. The results indicate that a primed NLRP3 inflammasome system is maintained despite clinical stability and best available therapy, highlighting the need to further combat inflammation in patients with CCS.
Предметные рубрики MeSH
HumansNLR Family, Pyrin Domain-Containing 3 ProteinMaleFemaleMiddle AgedInflammasomesProspective StudiesAgedInterleukin-18Exercise TestCase-Control StudiesChronic DiseaseExercise TherapyExerciseNF-kappa BSignal TransductionInterleukin 1 Receptor Antagonist ProteinLeukocytes, MononuclearTime FactorsInterleukin-6Exercise Tolerance