Apolipoprotein A-I at the Interface of Vascular Inflammation and Arthritis
- arthritis, psoriatic
- arthritis, rheumatoid
- lupus erythematosus, systemic
- Lyme disease
Decreased high-density lipoprotein cholesterol (HDL-C) levels are associated with an increased risk of atherosclerosis and its atherothrombotic complications. This has spawned numerous randomized human atherosclerosis trials of measures to indirectly or directly elevate HDL to directly test the HDL hypothesis.1,2 HDL functions, beyond reverse cholesterol transport, include antithrombotic effects, stimulation of endothelial nitric oxide release, and shuttling of microRNAs. Moreover, HDL and its principal apolipoprotein A-I (apoA-I) suppress vascular inflammatory responses in experimental atherogenesis and arterial injury,3,4 though such effects seem modulated by genetic background.5 Significantly, primary extravascular inflammatory processes promote quantitative and qualitative modulation of HDL and apoA-I. This is exemplified by 3 conditions (rheumatoid arthritis [RA], systemic lupus erythematosus [SLE], and gout) in which there is coexisting inflammatory arthritis and increased susceptibility to atherosclerosis, but with differences in mechanisms affecting HDL levels and properties of plasma HDL (see Figure).