Increasing apoA-I production as a target for CHD risk reduction

Dyslipidemia leading to coronary heart diseases (CHD) enables venues to prevent or treat CHD by other strategies than only lowering serum LDL cholesterol (LDL-C) concentrations, which is currently the most frequently targeted change. Unlike LDL-C, elevated high-density lipoprotein cholesterol (HDL-C) concentrations may protect against the development of CHD as demonstrated in numerous large-scale epidemiological studies. In this review we describe that besides elevating serum HDL-C concentrations by increasing alpha-HDL particles, approaches to elevate HDL-C concentrations by increasing pre-beta HDL particle concentrations seems more attractive. Besides infusion of apoA-I(Milano), using apoA-I mimetics, or delipidation of alpha-HDL particles, elevating de novo apoA-I production may be a suitable target to functionally increase pre-beta HDL particle concentrations. Therefore, a detailed description of the molecular pathways underlying apoA-I synthesis and secretion, completed with an overview of known effects of pharmacological and nutritional compounds on apoA-I synthesis will be presented. This knowledge may ultimately be applied in developing dietary intervention strategies to elevate apoA-I production and serum HDL-C concentrations and consequently lower CHD risk

Effects of emulsified policosanols with different chain lengths on cholesterol metabolism in heterozygous LDL receptor-deficient mice.

Policosanol mixtures have been postulated as promising functional food ingredients to lower serum LDL cholesterol, and increase HDL cholesterol concentrations. We evaluated whether policosanol chain-length [tetracosanol (C24), hexacosanol (C26), octacosanol (C28), triacontanol (C30)] was relevant for its cholesterol lowering effects in heterozygous LDL-receptor deficient mice (LDLr +/-). In addition, effects of individual policosanols varying in chain-length and their respective long-chain fatty acids, and aldehydes on expression of genes involved in lipoprotein metabolism and apoA-I production, were evaluated in vitro. After a run-in period, LDLr +/- mice received experimental western-type diets without policosanols, or similar diets enriched with 30 mg/100 g individual policosanol, or a natural policosanol mixture (Lesstanol60). No significant effects on serum cholesterol concentrations, lipoprotein profiles, or hepatic and small-intestinal mRNA expression of lipoprotein metabolism related genes were found for any of the policosanol diets. In HepG2 and differentiated CaCo-2 cells, policosanols did not change de novo apoA-I protein production. In HepG2 cells, Lesstanol60 elevated gene expression of ABCA1 and HMG CoA synthase-1, however since effects were not observed in vivo, absorption of the responsible components seems to low. We conclude that individual policosanols as well as Lesstanol60 have no potential in reducing CHD risk through effects on serum lipoprotein concentrations