Atherosclerosis is a global concern and is a leading cause of cardiovascular events.1 Studies have shown that childhood cholesterol levels predict adult cholesterol levels, suggesting that children with high cholesterol levels are at high risk for atherosclerosis and early onset of coronary heart disease (CHD). Endothelial dysfunction, an important early event in the development of CHD,is present in children with high cholesterol levels before the formation of plagues within the arteries. The primary management of high cholesterol is lifestyle modification such as diet. Studies have shown that the Mediterranean diet is effective for the prevention of CHD. The cardioprotective effect of the Mediterranean diet may be attributed to the anti-oxidative and anti-inflammatory activities of the polyphenols abundant in the Mediterranean diet. Polyphenols are also known to improve vascular function by increasing the bioavailability of nitric oxide (NO), a potent endothelial-derived vasodilator. Several lines of evidence indicate that omega-3 fatty acid supplements also enhance endothelial function by stimulating release of NO from the endothelial cells, decreasing triglyceride concentration, and inhibiting platelet aggregation. MicroRNAs (miRNAs) are short noncoding RNA molecules that have approximately 22 nucleotides in length. They regulate gene expression by binding to complementary sites on the 3 untranslated regions of target mRNAs, which causes the mRNA to be degraded and translated less. As negative regulators of gene expression, miRNAs are crucially involved in a variety of biological processes in health and diseases including cardiovascular disease. Surprisingly, miRNAs are detected in serum and plasma, and they are known to be remarkably stable. Recent studies have revealed that these extracellular microRNAs are differently expressed in healthy people and those with hyperlipidemia or CHD. For example, miRNA -122 and miRNA-370 are significantly increased in hyperlipidemia patients compared with controls. According to in-vivo and in-vitro studies, miRNA-122 and miR-370 play important roles in fatty acid synthesis and oxidation. Another study has shown that circulating levels of vascular miRNAs (miRNA 126, miRNA17, miRNA92a), inflammation-associated miRNA (miRNA 155), and smooth muscle-enriched miRNA (miRNA 145) are significantly lower in patient with CHD compared with healthy controls. Studies that have investigated the impact of dietary supplementation on miRNA expression are very limited. Nevertheless, a few in-vitro studies have demonstrated that omega-3 fatty acids significantly inhibit expression of miRNA-21 which is known to contribute to the growth and metastasis of tumors originating from breast cancer cells. Interstingly, proanthocyanidin extracted from grape seed and cocoa upregulated miR-197,25 of which a target gene plays a central role in liver lipid production. Despite the great potential of dietary interventions on modification of miRNA expression, little is known how the diet changes miRNA expression. Understanding the effect of dietary factors on miRNA expression and function may provide insight into therapeutic strategies to reduce the burden of hyperlipidemia in children.