Vienna/Innsbruck (FWF) - 30 to 50 % of all deaths in western industrialised nations are caused by arteriosclerosis according to a WHO study. While cholesterol has been known to be a risk factor for years, less attention has been paid to another factor, apolipoprotein A-IV (or, for short, apoA-IV). In a project sponsored by the Austrian Science Fund (FWF), Florian Kronenberg from the Institute of Medical Biology and Human Genetics at Innsbruck University and his team have now detected a relationship between low apoA-IV concentrations and coronary vascular diseases in humans.
Elevated cholesterol levels in the blood are conducive to the formation of arteriosclerosis. A lack of exercise, cigarette smoking, excessive food intake etc. are the external reasons for lipid metabolism problems, which may cause cholesterol to be deposited on the walls of blood vessels. These relationships have long been known and taken into account in medical practice. Recently, however, there have been indications that apoA-IV may have antiatherogenic properties and thus may inhibit the degeneration of blood vessel walls in cases of arteriosclerosis. ApoA-IV participates in several steps of the process, which transports cholesterol back to the liver and other organs for metabolisation. Mice with excessive apoA-IV levels have been shown to be far less inclined to develop arteriosclerosis. After cross-breeding these animals with mice with a strong genetic predisposition to arteriosclerosis, the extent of the disease was significantly reduced in the next generation. "This is reason enough for us to study this protein more closely", says Kronenberg. "First, we have to identify the variables influencing apoA-IV concentration".
ApoA-IV - a new target parameter?
In order to determine these influencing factors Kronenberg measured the apoA-IV levels of about 1000 persons and related the results to detailed information on diet, physical condition, laboratory parameters etc. within the framework of the "Bruneck Study". In this way it was possible to identify both the influencing variables and the extent of influence. Kronenberg: "We were able show that kidney diseases, for instance, cause a significant increase in apoA-IV concentrations. High apoA-IV levels can therefore be used as a parameter for the early recognition of kidney diseases". Kronenberg also wants to determine whether apoA-IV actually plays a direct role in the formation and development of arteriosclerosis. If this is the case apoA-IV might serve, for instance, as a target for drugs which increase apoA-IV concentrations in a targeted manner and thus reduce the risk of arteriosclerosis. In this context Kronenberg concentrates his efforts on the question of whether and how apoA-IV concentrations are genetically controlled: "Our aim is to find the genes that influence apoA-IV levels".
Dr. Florian Kronenberg
Institute of Medical Biology and Human Genetics
University of Innsbruck
T ++ 43 0512 507 3474
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Vienna, 19 July 2002