Inhibitory Effects of Grape Seed Procyanidins on Foam Cell Formation in Vitro

Human and animal studies have demonstrated that procyanidin-rich diets reduce the risk of cardiovascular diseases and atherosclerosis. Some beneficial effects have been attributed to the well-known antioxidant activity of procyanidins. This study investigated another potential corrective role of procyanidins in cholesterol flux and inflammation in macrophage-derived foam cells. RAW 264.7 macrophages were cultured with moderately oxidized LDL (oxLDL), minimally oxidized LDL (moxLDL), or LPS (0.5 mu g/mL) and oxLDL (LPS + oxLDL) to induce foam cells. Then, cells were treated with procyanidins derived from grape seed (PE, 45 mu g/mL) for the last 12 h of incubation with the different lipoproteins (25 mu g/mL). After lipid extraction, it was determined that total and esterified cholesterol and triglyceride accumulations in foam cells were increased by lipoprotein treatment but reduced by PE incubation. To asses the effect of PE on gene expression, the relative mRNA levels of CD36, ABCA1, iNOS, COX-2, and I kappa B alpha were determined by RT-PCR. It was shown that PE reduced the oxLDL scavenger receptor expression (CD36) and enhanced ATIP-binding cassette A1 (ABCA1) expression, a key regulator of macrophage cholesterol efflux. PE also down-regulated inflammatory-related genes such as inducible nitric oxide synthase (iNOS) and kappa beta inhibitor-alpha (I kappa B alpha) without modifying COX-2 expression. In conclusion, evidence is provided that procyanidins may attenuate the development of foam cell formation by reducing cholesterol accumulation and modulating the expression of key genes in cholesterol flux and inflammation.