Lipid Immunometabolism in Autoimmune Rheumatic Diseases: Mechanistic Links Between Chronic Inflammation, Lipoprotein...

Area of Science:

• Rheumatology
• Immunology
• Cardiovascular Medicine

Background:

• Autoimmune rheumatic diseases (ARDs) like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are linked to increased cardiovascular disease (CVD) risk.
• Conventional lipid profiles often fail to fully capture this heightened CVD risk in ARD patients, a phenomenon sometimes termed the 'lipid paradox'.
• The lipid paradox describes situations where lower cholesterol levels paradoxically coexist with elevated vascular risk, particularly during active inflammation.

Purpose of the Study:

• To explore the mechanistic links between systemic inflammation in ARDs and cardiovascular risk.
• To investigate how inflammatory cytokines influence lipoprotein metabolism and function.
• To synthesize evidence on how these inflammatory pathways contribute to endothelial dysfunction and thrombo-inflammation in ARDs.

Main Methods:

• Review and synthesis of existing evidence on inflammatory cytokines and their impact on lipid metabolism.
• Analysis of mechanistic axes including cytokine effects on high-density lipoproteins (HDL) and apolipoprotein-B (ApoB) particles.
• Extrapolation of findings from experimental atherosclerosis and immune-cell metabolism where direct ARD evidence is limited.

Main Results:

• Key inflammatory cytokines (e.g., IL-6, TNF-α) remodel lipoprotein metabolism, diminishing HDL's protective functions and potentially making it pro-inflammatory.
• Oxidation and modification of ApoB particles link lipid changes to autoimmune processes.
• Inflammasome activation and immune cell metabolic alterations contribute to endothelial dysfunction and thrombo-inflammation, key drivers of CVD in ARDs.

Conclusions:

• Systemic inflammation in ARDs significantly alters lipoprotein function and metabolism, contributing to cardiovascular risk.
• Standard lipid panels may underestimate cardiovascular risk in patients with active inflammatory rheumatic diseases.
• Understanding these inflammatory mechanisms is crucial for accurate risk assessment and management in ARDs.