Table 4.
Therapeutic effect of pattern-recognition receptors inhibition and their inflammatory modulation in CRS type 4.
| PRR Type | DAMPs or tDAMPs That Activate PRRs | Associated Cytokines/ Chemokines |
Therapeutic Effect of the PPR Inhibition in the CRS Type 4 | References |
|---|---|---|---|---|
| NLRP3 | ↑ ROS Extracellular ATP Cardiolipin EVs Apoptotic bodies |
IL-1β, IL-18, TGF-β, TNF-α CCL8, CXCL10 |
↓ Cardiac dysfunction ↓ Cardiac fibrosis ↓ Cardiac hypertrophy |
[121,135,136,142,144,145,146,149,158,192]. |
| TLR2/ TLR4 |
Cell debris Nucleic acid fragments ↑ Oxidative products ↑ Uremic toxins HSPs |
IL-1β, IL-18, IFN-γ, IL-6, TNF-α CCL2, CCL8 |
↓ Cardiac hypertrophy ↓ BNP levels ↓ α-actin levels |
[45,71,131,145,167,168,169,170,171,172,173,174,175,176]. |
| TLR9 | mtDNA EVs |
IL-1β, IL-18, IL-6 Chemokines? |
? | [180,181,182,187,189,193]. |
| cGAS-STING | dsDNA Neutrophil DNA-protein complexes mtDNA |
IL-18, IL-1β CCL8, CXCL10 |
↓ Cardiac hypertrophy | [44,217,218,226,233]. |
Abbreviations: BNP: brain natriuretic peptide; dsDNA: double-stranded DNA; EVs: extracellular vesicles; HSPs: heat shock proteins; mtDNA: mitochondrial DNA; PRR: pattern-recognition receptor; ROS: reactive oxygen species. Symbols: ↑ increase, ↓ decrease, ? unknown effect.