Inflammatory lipids as a target for therapy in the rheumatic diseases.
As patients with autoimmune rheumatic diseases live longer due to improved therapies and preventive measures, death and disability from cardiovascular events are increasing. Patients with rheumatoid arthritis and systemic lupus erythematosus have an increased risk of atherosclerosis that persists even after accounting for traditional cardiac risk factors. Recent studies strongly suggest that the mechanism is due in part to increased levels of oxidized lipids (such as oxidized low density lipoprotein and pro-inflammatory high density lipoproteins) which cause the inflammatory cascade that ultimately leads to plaque formation. The objective of this review is to discuss how inflammatory lipids contribute to the increased risk of atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus, as well as to propose that these oxidized lipids are a rational target for therapeutic intervention in autoimmune diseases. Published literature was examined to review treatments for pro-inflammatory lipids in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. In conclusion, it is possible that these oxidized lipids may also contribute to increased disease manifestations in rheumatic conditions. Several new and existing therapies, including statins and high density lipoprotein-associated protein peptide mimetics such as D-4F (apoA-1) target these oxidized lipids and may be useful in both preventing atherosclerosis and treating inflammation in patients with rheumatic diseases.
McMahon
Maureen
M
David Geffen School of Medicine at the University of California Los Angeles, Division of Rheumatology, Department of Medicine, UCLA Rheumatology, 1000 Veteran Avenue, Los Angeles, CA 90095-1670, USA. mmcmahon@mednet.ucla.edu
Brahn
Ernest
E
D000818:Animals; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D008074:Lipoproteins / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D010084:Oxidation-Reduction; D012216:Rheumatic Diseases / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome
D016632:Apolipoprotein A-I; C465468:D-4F peptide; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins