The other side of HDL
The role of the HDL protein in atherosclerosis is more complex role than previously thought. While HDL indeed clears excess cholesterol from the bloodstream, a new study shows that it can also exhibit pro-inflammatory effects.
It is generally thought that high levels of the protein HDL (High Density Lipoprotein) reduce the risk of atherosclerosis, because it depletes cholesterol from the tissues by transporting it to the liver for degradation. In addition, HDL acts on several cell types to curb inflammatory reactions. But LMU’s Dr. Emiel van der Vorst (Institute for Cardiovascular Prevention), together with Dutch colleagues, has now shown that, in relation to atherosclerosis, not all of HDL’s actions can be viewed in a wholly positive light. The researchers report their results in the journal Cell Metabolism.
Inflammation reactions initiated by macrophages are a major contributor to the progression of atherosclerosis. Macrophages are phagocytic cells of the immune system that engulf and degrade cell debris as well as the fat-rich deposits (plaque) that promote the development of atherosclerosis. However, when they “overeat,” macrophages release signals that initiate an inflammation response. Since HDL is known to possess anti-inflammatory activity, van der Vorst and his collaborators assumed that it also counteracts this process. “To our surprise, however, our study showed that HDL has the opposite effect on activated macrophages,” says van der Vorst. “We looked at several subtypes of HDL and macrophages from various sources, both in vivo and in vitro, and in each case we found that HDL actually augments the pro-inflammatory effects of macrophages.“
The authors believe that these findings can -- at least in part -- account for the fact that clinical studies of the therapeutic efficacy of high levels of HDL in patients with atherosclerosis have been disappointing. “Its pro-inflammatory action on macrophages could simply override the positive effects of HDL,” van der Vorst points out. The researchers emphasize, however, that their results do not imply that HDL should now be recast as the villain in the piece. Its overall effect is the result of complex interactions between diverse cell types, and these interactions vary according to the precise nature and stage of the disease, and from one individual to the next. Subsequent studies will focus on these interactions, with a view to finding new strategies for the use of HDL-based approaches to the treatment of atherosclerosis.