High-density lipoprotein (HDL), known colloquially as "good cholesterol", protects against dangerous deposits in the arteries. An important function of HDL is its anti-inflammatory properties. An international research team at the Institute of Innate Immunity at the University Hospital of Bonn and the LIMES Institute at the University of Bonn has identified a central switch by which HDL controls the inflammatory response. The results are presented in the current issue of "Nature Immunology".
High cholesterol levels are seen as a cause of dangerous deposits in the bloodstream, which lead to hardening of the arteries (atherosclerosis). As a consequence, thrombosis, strokes, and heart attacks can develop, which are among the leading causes of death in Western society. Low-density lipoprotein (LDL) is commonly referred to as the "bad cholesterol", because it promotes atherosclerosis. In contrast, the "good cholesterol", high-density lipoprotein (HDL), helps transport excess cholesterol out of the bloodstream and can counteract an inflammatory reaction in damaged vessel walls.
"It has long been known that HDL has a protective function in cardiovascular diseases that are based on atherosclerosis", reports Prof. Eicke Latz, Director of the Institute of Innate Immunity at the University of Bonn and who is further affiliated with the German Center for Neurodegenerative Diseases (DZNE) and the University of Massachusetts Medical School in the USA. "The molecular causes to which this protective effect of HDL can be attributed were unclear until now". For instance, studies had shown that therapies that simply increase HDL levels in the blood of patients are not sufficient to reduce the incidence of atherosclerosis. HDL has anti-inflammatory effects on immune cells - however the mechanisms have remained unclear until now. The research group has now investigated how HDL acts upon inflammatory processes.
Bioinformatics approach revealed a candidate gene
Principle investigators Dr. Dominic De Nardo and Larisa I. Labzin are both Australians currently training in the lab of Prof. Eicke Latz. In collaboration with other working groups of the University of Bonn, an international research team from Japan, Australia, China, the USA, and Germany has identified how HDL acts to prevent chronic inflammation. In a very extensive study over a period of about three years, the group performed experiments in human and mouse cells, to determine which genes are regulated by high HDL levels. "At first, we were really just feeling around in the dark", reports Prof. Latz. Close cooperation with the working group of Prof. Joachim L. Schultze of the Life and Medical Sciences (LIMES) Institute of the University of Bonn finally got the scientists on the right track. "With the aid of genomic and bioinformatics approaches, we were able to filter out a candidate gene from the wealth of regulated genes", adds Prof. Schultze.