Gottfried Schatz Research Center | Molecular Biology and Biochemistry

ATHEROGENESIS: Genetic, epigenetic and metabolic risk factors.

We focus since years on the identification and characterization of factors that are involved in the transcriptional and post-transcriptional processes of relevant genes in lipoprotein and cholesterol metabolism. Of particular interest is the investigation of the function and metabolism of Lp(a) one of the most atherogenic lipoprotein. Challenges in this topic are guided by the fact that virtually nothing is known on the physiological function, the biosynthesis and catabolism of Lp(a). There are also only few animal models or permanent cell cultures that may be used for studying these processes. We therefore put some emphasis on the cultivation of permanent cell cultures that express apo(a) and that may be useful tools for addressing cellular events in apo(a) biosynthesis and Lp(a) catabolism. The results may guide to the development of new drugs to interfere with elevated Lp(a) plasma concentrations. Another topic that interests us most is the cellular homeostasis of cholesterol. Although humans ingest sufficient amounts of cholesterol in diets to cover their needs, almost any human cell is able for sufficient de novo cholesterol biosynthesis. Yet, any excess of cholesterol is deleterious and leads to deposition in different organs giving rise to atherosclerotic plaques and vascular diseases followed by cell death, myocardial infarction and stroke. The fascinating aspects in studying cholesterol metabolism are, that the factors regulating cholesterol homeostasis differ quite significantly from organ to organ. This is true for the brain, the liver, the intestine, adipose tissue, macrophages, cholesterol in the blood circulation and more. Genes involved in cholesterol metabolism are therefore tightly regulated by nuclear receptors, and transcription factors. Lately it turned out that micro-RNA’s an LncRNAs in addition are important for cholesterol homeostasis. Although much has been learned in recent years, there are still ample gaps in our knowledge that need to be unraveled. 

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