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SP0145 HDL as a Pro-Inflammatory Agent
  1. M. Mcmahon1
  1. 1Rheumatology, UCLA David Geffen School of Medicine, Los Angeles, United States

Abstract

Although HDL levels are traditionally inversely related to atherosclerosis, the relationship is complex and involves both HDL quantity and function. HDL has been described as “chameleon-like,” anti-inflammatory in the basal state and pro-inflammatory (piHDL) during an acute-phase response. In piHDL, levels of anti-inflammatory components of HDL such as apo A-I and HDL-associated paraoxonase activity are reduced. Additionally, acute phase HDL is greatly enriched in acute phase reactants such as serum amyloid A. Dysfunctional piHDL cannot perform many of the anti-atherogenic functions of normal HDL; it cannot prevent oxidation of LDL-C and actually increases it, leading to impairment of reverse cholesterol transport and increased recruitment of monocytes to the cell wall. Oxidatively modified HDL also stimulates an enhanced inflammatory response, including upregulation of the adhesion molecule VCAM-1 on endothelial cells.

Chronic inflammatory responses and oxidative stress may be a mechanism for HDL dysfunction in patients with rheumatic diseases. Indeed, our group has found that HDL function is abnormal in many SLE and RA patients; 45% of women with SLE, compared to 20% of rheumatoid arthritis patients and 4% of controls, had pro-inflammatory HDL that was not only unable to prevent oxidation of LDL but caused increased levels of oxidation. Subsequent studies have indicated that 85% of SLE women with plaque on carotid ultrasound have piHDL, indicating that piHDL may be a biomarker of risk for atherosclerosis in SLE. In addition, HDL appear to be dysfunctional in primary antiphospholipid syndrome. Accumulating evidence suggests that dysfunctional pro-inflammatory HDL may not only be a biomarker for increased atherosclerotic risk but may also directly contribute to systemic inflammation and organ manifestations in patients with rheumatic diseases.

Disclosure of Interest None Declared

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