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 seem more attractive. Besides infusion of apoA-I-Milano, using apoA-I mimetics, or delipidation of a-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 wilt 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. (C) 2007 Elsevier B.V. All rights reserved.