ATVB In Focus
Lipoproteins, Inflammation, and Atherosclerosis
The brief review by Pennacchio and Rubin1 in this issue of Arteriosclerosis, Thrombosis, and Vascular Biology is the first of the Series, which highlights how innovative technology and research is breathing new life into the role of lipoproteins in health and disease. Lipoproteins have been around for a long time. Primitive lipoproteins found in worms (Caenorhabditis elegans) and flies (Drosophila melanogaster), the so-called lipovitellins, are closely related mammalian lipoproteins. Lipoprotein research has also been with us for quite a while. In the early 1950s, the pioneering work of the Lawrence Berkeley National Laboratory used ultracentrifugation to fractionate and classify the plasma lipoproteins. In the ensuing years, much has been learned about the role of lipoproteins in health and disease. Oxidized LDL is established as the argent provocateur of the arteriosclerosis. HDL is atheroprotective through its role in reverse cholesterol transport and its anti-inflammatory properties. However, with the advent and fabulous success of the statin drugs, a view emerged that lipoprotein research had reached its sunset. If there is any lingering doubt that this not the case, I am convinced this series will change this view.
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It seems highly appropriate that the first article in this new series of reviews should come from the Lawrence Berkeley National Laboratory. In their review, Pennacchio and Rubin1 show that even today the lipoprotein system is full of surprises. Nobody would have guessed that the sequence of the human genome would reveal an overlooked apolipoprotein in the apoAI/CIII/AIV cluster on chromosome 11q. By use of state of the art genome sequence analysis tools, Pennacchio and Rubin1 identified a completely new apolipoprotein gene, which they aptly called apoAV. The apoAV is closely related to apoAIV and apoAI. It seems to float on HDL particles while having a clear link to triglyceride metabolism and to genetic variation in triglyceride levels.
Other reviews in this Series will delve deep into the role of lipoproteins in the pathogenesis of arteriosclerosis and the inflammatory processes that drive it. The series will focus heavily on animal models as well as human research.