We found that MI triggered NLRP3 inflammasome activation leading to conversion of interleukin-1β (IL-1β) and IL-18 into their active mature forms in the heart, which could expand the infarct size and drive cardiac dysfunction.
-511C/T IL-1beta gene polymorphism affects the risk of MI and ischemic stroke at young age and the response of mononuclear cells to inflammatory stimulation.
The IL-6C and APOE epsilon4 alleles were independently associated with a mild or moderate increased risk of MI, whilst the allele C of the IL-1beta was not independently linked to MI risk.
Long-term effects of carvedilol on left ventricular function, remodeling, and expression of cardiac cytokines after large myocardial infarction in the rat.
The objective of the study is to assess the modulatory effect of IL-1 genotypes on risk mediated by Lp(a) METHODS: We assessed whether IL-1 genotypes modulate the effect of Lp(a) on major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke/transient ischemic attack) and angiographically determined coronary artery disease (CAD).
Cases had higher levels of IL-1Ra at all time-points leading up to first-time MI, and higher levels of IL-1Ra were associated with approximately 1.5-fold increased risk of MI, supporting the rationale to target IL-1 activation in order to reduce cardiovascular risk in PWH.
In conclusion, our data indicate that IL-1β-511TT/CC influence on the risk of myocardial infarction and ischemic stroke at young age through NF-κB, iNOS, MMP-2 and Bax.
Immunomodulatory interventions in myocardial infarction and heart failure: a systematic review of clinical trials and meta-analysis of IL-1 inhibition.
Systemic administration of 2-deoxyglucose after rodent MI normalized the hyperpolarized [1-<sup>13</sup>C]lactate signal in healing myocardial segments at day 3 and also caused dose-dependent improvement in IL (interleukin)-1β expression in infarct tissue without impairing the production of key reparative cytokines.
Accordingly, CANTOS trial using an interleukin-1 beta antibody confirmed that inflammatory cytokines contribute to the occurrence of myocardial infarction and cardiac death independent of changes in lipids.
A similar trend was identified for the expression of NF-κB, IL-1β and MMP-2, which was significantly increased in the MI group compared with that in the sham group (P<0.01), while it was significantly decreased in the MG and PDTC groups compared with that in the MI group (P<0.01).
Together, the data indicated that the knockdown of Mincle in microglia within the PVN prevents VAs by attenuating sympathetic hyperactivity and ventricular susceptibility, in part by inhibiting its downstream NLRP3/IL-1β axis following MI.
Furthermore, a recent Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) trial revealed the efficacy of IL-1β inhibition in preventing recurrent cardiovascular events in patients with MI.
Transcript levels of the pro-inflammatory cytokines interleukin-6 and interleukin-1β were upregulated in hearts of vehicle treated animals compared to mice without MI.
The CANTOS trial (Canakinumab Antiinflammatory Thrombosis Outcome Study) showed that antagonism of interleukin (IL)-1β reduces coronary heart disease in patients with a previous myocardial infarction and evidence of systemic inflammation, indicating that pathways required for IL-1β secretion increase cardiovascular risk.