Figure 1
NLRP3 inflammasome two-step activation: The first priming step is initiated by lipid and lipoprotein endogenous danger signals and pathogen associated molecules (FFA: free fatty acids; ox-LDL: oxidised low density lipoprotein; cholesterol crystals; LPS: lipopolysaccharide) and cytokines (IL-1β and TNFα) that signal through MyD88 to activate NF-ƘB mediated upregulation of NLRP3 and IL1B mRNA. The second signal is provided by diverse intracellular and extracellular molecules (ROS: reactive oxygen species released from mitochondria; lysosomally degraded ox-LDL and cholesterol crystals) and extracellular ATP binding to the K+ channel P2X7R. This initiates NLRP3 inflammasome component (NLRP3; ASC; Pro-caspase-1) assembly and activation of caspase-1 to cleave the pro-peptides and release IL-1β and IL-18. These mediators then prime other immune cells. Intracellular molecules are also released by pyroptopsis.
Source publication
Coronary Artery Disease (CAD) represents a major health burden worldwide. It is driven by chronic inflammation of the arterial vasculature
supplying the heart, in response to pro-inflammatory assaults such as high LDL cholesterol. The resultant atherosclerosis can cause occlusive
disease and acute cardiovascular events. The pro-inflammatory cytokin...
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Citations
The dysregulated immune system represents a major target for improving health outcomes in a range of chronic conditions. This chapter describes key changes in the immune system as we age and showcases its dysregulation across five chronic conditions including diabetes, cardiovascular disease, and cancer, highlighting dysregulated key immune system pathways and resultant inflammatory sequelae. Precision medicine aims to subdivide patients into different groups who will respond to specific treatments and could offer a novel way of addressing the complexity of immune system involvement in these conditions. The potential for precision medicine-led therapeutic strategies is discussed for each condition and considered in the context of multimorbidity.
