Cell-mediated lipoprotein transport: a novel anti-atherogenic concept.

Lipoprotein transport is thought to occur in the plasma compartment of the blood, where lipoproteins are modulated by various enzymatic reactions. Subsequently, lipoproteins can migrate through the endothelial barrier to the subendothelial space or are taken up by the liver. The interaction between pro-atherogenic (apoB-containing) lipoproteins and blood cells (especially monocytes and macrophages) in the subendothelial space is well known. This lipoprotein-inflammatory cell interplay is central in the development of the atherosclerotic plaque. In this review, a novel interaction is described between lipoproteins and both leukocytes and erythrocytes in the blood compartment. This lipoprotein-blood cell interaction may also be related to the process of atherosclerosis by inducing inflammatory changes in the case of leukocytes (pro-atherogenic) and as an anti-atherogenic transport-system by adherence to erythrocytes. Triglyceride rich lipoprotein (TRL)-mediated leukocyte activation can lead to an inflammatory situation with generation of oxidative stress and the production of cytokines, ultimately resulting in acute endothelial dysfunction. Binding of apoB containing lipoproteins to erythrocytes may be a potential anti-atherogenic mechanism protecting the vessel wall from the pro-inflammatory effects of these lipoproteins and also playing a role in the removal of these particles from the circulation. One of the proposed mechanisms of this interaction implies complement activation on the lipoprotein surface and binding to the Complement Receptor 1 (CR1) on erythrocytes and leukocytes, followed by clearance by the liver.

Dehydroepiandrosterone administration in humans: evidence based?

Dehydroepiandrosterone (DHEA) and its ester dehydroepiandrosterone sulphate (DHEAS) are produced by the adrenal glands. These hormones are inactive precursors that are transformed into active sex steroids in peripheral target tissues. After a peak in early adulthood, there is a marked decrease in plasma concentrations throughout adult life. These hormones are thought to affect mood and well-being, have neurosteroid effects and may influence the immune system. Animal experiments suggest that DHEA has many other effects, including anticancer, immune-enhancing, neurotropic and general antiageing effects, but information based on studies in humans is limited. In female patients with adrenal insufficiency, treatment with DHEA replacement doses of 20 to 50 mg results in improvements in mood, quality of life and libido. These studies usually lasted only a few months, so the effect of chronic DHEA treatment or its effectiveness in male patients is not known. Some studies suggest a favourable effect of pharmacological doses of DHEA in the treatment of depression. DHEA may have a very limited effect on cognitive function in elderly people, and some studies suggest a beneficial immunomodulatory effect of DHEA in patients with autoimmune diseases, but further studies are warranted before introducing DHEA for these indications in clinical practice.