Lipoproteins, cholesterol homeostasis and cardiac health

Abstract

Cholesterol is an essential substance involved in many functions, such as maintaining cell membranes, manufacturing vitamin D on surface of the skin, producing hormones, and possibly helping cell connections in the brain. When cholesterol levels rise in the blood, they can, however, have dangerous consequences. In particular, cholesterol has generated considerable notoriety for its causative role in atherosclerosis, the leading cause of death in developed countries around the world. Homeostasis of cholesterol is centered on the metabolism of lipoproteins, which mediate transport of the lipid to and from tissues. As a synopsis of the major events and proteins that manage lipoprotein homeostasis, this review contributes to the substantial attention that has recently been directed to this area. Despite intense scrutiny, the majority of phenotypic variation in total cholesterol and related traits eludes explanation by current genetic knowledge. This is somewhat disappointing considering heritability estimates have established these traits as highly genetic. Thus, the continued search for candidate genes, mutations, and mechanisms is vital to our understanding of heart disease at the molecular level. Furthermore, as marker development continues to predict risk of vascular illness, this knowledge has the potential to revolutionize treatment of this leading human disease.

Keywords: HDL; Homeostasis; LDL; candidate genes; cholesterol; expression; heart disease.

Figure 1

Reverse cholesterol transport pathway. Arrows are indicative of cholesterol movement and particle maturation. Cholesterol molecules are labeled “C”, and cholesterol esters “CE”.

Figure 2

Representation of the molecular activity of the LCAT protein.

Figure 3

Transport of exogenous cholesterol, and de novo cholesterol requires a diversity of lipoproteins and proteins, as shown above.

Figure 4

The LDLR structure contains three types of domain: LDLR-type A domains (LA), the epidermal growth factor precursor protein-like domain (EGPF), and a domain rich in serine and threonine residues. The endocytotic process is also shown, which yields free intracellular cholesterol [see with permission].