Plasma Membrane Lipids: An Important Binding Site for All Lipoprotein Classes.

Cholesterol is one of the main constituents of plasma membranes; thus, its supply is of utmost importance. This review covers the known mechanisms of cholesterol transfer from circulating lipoprotein particles to the plasma membrane, and vice versa. To achieve homeostasis, the human body utilizes cellular de novo synthesis and extracellular transport particles for supply of cholesterol and other lipids via the blood stream. These lipoprotein particles can be classified according to their density: chylomicrons, very low, low, and high-density lipoprotein (VLDL, LDL, and HDL, respectively). They deliver and receive their lipid loads, most importantly cholesterol, to and from cells by several redundant routes. Defects in one of these pathways (e.g., due to mutations in receptors) usually are not immediately fatal. Several redundant pathways, at least temporarily, compensate for the loss of one or more of them, but the defects trigger systemic diseases, such as atherosclerosis later on. Recently, intracellular membrane-membrane contact sites were shown to be involved in intracellular cholesterol transfer and the plasma membrane itself has been proposed to act as a binding site for lipoprotein-mediated cargo unloading.

Cholesterol transfer at the plasma membrane.

Cholesterol homeostasis is of central importance for life. Therefore, cells have developed a divergent set of pathways to meet their cholesterol needs. In this review, we focus on the direct transfer of cholesterol from lipoprotein particles to the cell membrane. More molecular details on the transfer of lipoprotein-derived lipids were gained by recent studies using phospholipid bilayers. While amphiphilic lipids are transferred right after contact of the lipoprotein particle with the membrane, the transfer of core lipids is restricted. Amphiphilic lipid transfer gains special importance in genetic diseases impairing lipoprotein metabolism like familial hypercholesterolemia. Taken together, these data indicate that there is a constant exchange of amphiphilic lipids between lipoprotein particles and the cell membrane.

Profound Changes in Sex Hormone Levels during Cross-Sex Hormone Therapy of Transsexuals do not Alter Serum Cholesterol Acceptor Capacity.

INTRODUCTION: Men and postmenopausal women exhibit a higher risk for atherosclerosis than premenopausal women. These differences were often attributed to sex steroids, but the role of estrogen and testosterone in atherosclerosis are more complex than anticipated. Cross-sex hormone therapy of transsexuals is an interesting model, which has been used to study hormonal effects on serum lipid profile, insulin resistance, and body composition. However, studies on macrophage cholesterol efflux, the first step in reverse cholesterol transport, are not available. AIM: The aim of this study was to evaluate the effect of cross-sex hormone therapy in transsexuals on the capacity of serum to accept cholesterol from macrophages. METHODS: Cholesterol acceptor capacity (CAC) of serum from transsexuals before and after at least 6 months of hormone treatment was measured using macrophage tissue culture models. MAIN OUTCOME MEASURES: CAC of serum using the human acute monocytic leukemia cell line (THP-1 cells). RESULTS: Unexpectedly, the CAC of serum from male to female (MtF) transsexuals was not increased, but decreased after hormone therapy. Serum from female to male (FtM) transsexuals showed no changes in CAC. CONCLUSIONS: Despite drastic changes in hormone status, no increase in CAC was detected in MtF patients, and no alteration in CAC was seen in FtM patients. These data further challenge the traditional view that estrogen and testosterone exert beneficial and detrimental effects, respectively, on lipoprotein metabolism and ultimately atherosclerosis.