ATLANTA—Rheumatologists are well aware that patients with rheumatoid arthritis (RA) and other chronic inflammatory disorders are at an increased risk of developing cardiovascular disease. It has also been established that high-density lipoprotein (HDL) levels correlate inversely with cardiovascular risk. Recent research, such as the study by Carpintero et al, which was led by a team of Swiss, Italian, and Australian investigators, have begun to narrow in on HDL’s ability to interfere with T-cell binding to monocytes, inhibiting production of proinflammatory cytokines.1
These discoveries have led to an important question: Might the intersection of cholesterol metabolism, atherogenesis, and inflammatory signaling offer a potential pathway for interventional strategies to combat inflammatory disease? These were the questions addressed by the research scientists who presented at the session, “A Critical Role for Lipid Metabolism in the Interplay between Atherosclerosis and Autoimmune Disorders.” [Editor’s Note: This session was recorded and is available via ACR SessionSelect at www.rheumatology.org.]
Kerry-Anne Rye, PhD, a professor at the University of Sydney, Australia, addressed the question: “Is it possible to use HDL to attenuate arthritis?” She and her group have conducted experiments at the Heart Research Institute of Sydney, where she is associate director, aimed at exploring a possible use of HDL to counteract the inflammatory processes that result in joint erosion.
Dr. Rye prefaced her presentation of her group’s current work with a succinct description of HDLs. Although we commonly use one term to refer to high-density lipoproteins, she noted, they do not comprise a single entity. Rather, HDLs are a complex series of subpopulations of particles, all of which are continually being interconverted from one to another by a range of factors in the circulation. HDLs, she said, “start off as discoidal particles consisting of a phospholipid bilayer surrounded by apolipoproteins,” and are classified according to the presence of one or both of their main constituent apolipoproteins, apoA-1 and apoA-2.
Able to Alleviate Inflammation?
One of the antiatherogenic functions of HDL is its ability to efflux cholesterol, especially from macrophages in the artery walls. HDL also has antithrombotic, antiinflammatory, and antioxidant properties. There may be other beneficial properties of HDL which have yet to be identified, Dr. Rye said.
To investigate HDL’s possible antiinflammatory functions, Dr. Rye’s group used a female Lewis rat model of induced arthritis. The rats received a single intraperitoneal injection of PG-PS, a bacterial cell wall component consisting of peptidoglycan and polysaccharide chains that induces a systemic inflammatory response. All animals exhibited a biphasic inflammatory response after the injection of PG-PS. The acute phase was characterized by joint swelling (rated on a score of 0 to 5). After a brief remission period (Days Seven to Nine following injection), inflammation returned, and entered a chronic phase until Day 21, when the study ended.
