Effects of Dietary Interventions on Serum and Macrophage Atherogenicity

Overview

While previous atherosclerosis-related studies have focused mainly on the atherogenicity of lipids, the proposed study aims to investigate the effects of other dietary factors, i.e. monosaccharides, disaccharides, amino acids, or artificial sweeteners, on the atherogenicity of serum or macrophages. Findings from the current proposed study may shed light on yet unknown mechanisms by which the above dietary factors could affect atherosclerosis development and CVD risk and hence could possibly assist in the future development of anti-atherogenic strategies.

Atherosclerosis is the underlying cause of cardiovascular diseases (CVD), the major cause of death worldwide. Atherosclerosis is an inflammatory disease of the arteries in which activated macrophages are abundant in the atherosclerotic lesions. Macrophages play key roles during early atherogenesis. After differentiating from peripheral blood monocytes, the formed intimal macrophages take up oxidized/modified lipoproteins and are transformed into lipid-rich foam cells, the hallmark feature of early atherogenesis. In addition to lipoprotein uptake, lipid accumulation in macrophages can also result from alterations in cellular lipid metabolism, e.g. attenuated reverse lipid transport or enhanced rates of lipid biosynthesis. CVD and atherosclerosis development are significantly affected by nutritional factors. Although much progress has been made in understanding the role of different lipids (fatty acids, cholesterol, phospholipids or triglycerides) in atherosclerosis development and macrophage foam-cell formation, little is known about the potential impact of other nutrients, i.e. sugars or amino acids. For instance, hyperglycemia is known to enhance atherosclerosis development, and high glucose levels increases macrophage atherogenicity via pro-inflammatory and oxidative stress-related mechanisms. However, the role of monosaccharides other than glucose (fructose, galactose or mannose) and that of various disaccharides (maltose, sucrose or lactose) in macrophage foam-cell formation, the key event during early atherogenesis, is currently unknown. As for amino acids, a specific subgroup - the branched-chain amino acids (BCAAs), has recently been associated with increased CVD risk. The BCAA subgroup, composed of leucine, isoleucine, and valine, is characterized by an aliphatic structure of their side chains and by a common catabolic pathway. Recent reports have demonstrated an association between BCAAs, CVD and coronary artery disease (CAD). Serum BCAA levels have been positively associated with various CAD risk factors and with the development as well as the severity of CAD, even after controlling for other risk factors. Nevertheless, the role of BCAAs in atherosclerosis development and macrophage foam-cell formation is currently unclear. In recent decades, the availability and the consumption of various artificial sweeteners have increased considerably. In the USA for instance, approximately 30% of adults and 15% of children, report consumption of artificial sweeteners. Although the consumption of artificial sweeteners was previously associated with elevated risk for coronary heart disease (CHD), the effects of different artificial sweeteners, e.g. saccharin, aspartame, sucralose, steviol, cyclamate, and mannitol, on atherosclerosis development and their possible impact on macrophage foam-cell formation have not been investigated yet..