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Abstract
Cardiovascular diseases (CVDs), the leading cause of death worldwide, are associated with high plasma cholesterol levels. The conversion of cholesterol to bile acids (BAs) accounts for about 50 % of total cholesterol elimination from the body. This phenomenon occurs in the liver and is regulated by nuclear receptors such as hepatocyte nuclear factor-4α (HNF-4α). Therefore, special emphasis is given to HNF-4α properties and its multifunctional role, particularly in the conversion of cholesterol to BAs. HNF-4α is a highly conserved transcription factor that has the potential capacity to transactivate a vast number of genes, including CYP7 which codes for cholesterol 7α-hydroxylase (CYP7A1; EC 1.14.13.17), the rate-limiting enzyme of BA biosynthesis. The fact that HNF-4α transactivation potential can be modulated via phosporylation is of particular interest. Additional findings on structural and functional characteristics of HNF-4α may eventually present alternatives to control the levels of cholesterol in the body and consequently reduce the risk of CVDs.