NLRP3 downregulation by apabetalone reference, page 14:
Apologies for the formating of the text I copy/pasted
My boldings

https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-020-00943-0

Upon stimulation with cytokines and PRR agonists,

monocytes and macrophages activate the infammasome

pathway, which is responsible for the production of the mature secreted form of IL-1β, a major pro-atherosclerotic cytokine [50]. IFNγ contributes to high IL1B gene

expression only when combined with secondary stimuli

[80]. Consistent with published data [80], IFNγ did not

change the IL1B transcript abundance as a single agent

(data not shown), but it enhanced the IL-1β protein

secretion by 2.7-fold in DM2+CVD monocytes (Fig. 6).

This induction was countered by apabetalone treatment

(84% reduction). IL-1β is synthesized by monocytes in

its inactive form (pro-IL-1β), which is then converted

into its active mature form by the NLRP3 infammasome-associated caspase 1 protease (encoded by CASP1

gene) [50]. Apabetalone (25 μM) downregulated CASP1

gene transcription in DM2+CVD monocytes in nonstimulated (Table 2) and stimulated (Table 3) conditions,

potentially explaining the observed decrease in IL-1β.

The severity of atherosclerosis correlates with infammasome activity and NLRP3/caspase 1-mediated generation

of IL-1β and IL-1α in human atherosclerotic plaque [81].

Interestingly, the anti-IL-1β monoclonal antibody canakinumab reduced the risk of MACE for CVD patients by

15% in 3.7  years, independently of lipid lowering [82].

This proof-of-concept study demonstrated that countering infammasome-mediated infammation signifcantly reduces residual CVD risk, promoting the development of new anti-infammatory therapeutic agents.