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 microg/mL) and oxLDL (LPS + oxLDL) to induce foam cells. Then, cells were treated with procyanidins derived from grape seed (PE, 45 microg/mL) for the last 12 h of incubation with the different lipoproteins (25 microg/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 IkappaBalpha were determined by RT-PCR. It was shown that PE reduced the oxLDL scavenger receptor expression (CD36) and enhanced ATP-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 (IkappaBalpha) 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.
Terra
Ximena
X
Department of Biochemistry and Biotechnology, Unitat d'Enologia del Centre de Referencia en Tecnologia dels Aliments de la Generalitat de Catalunya, Universitat Rovira i Virgili, Tarragona, Spain.
Fernández-Larrea
Juan
J
Pujadas
Gerard
G
Ardèvol
Anna
A
Bladé
Cinta
C
Salvadó
Josepa
J
Arola
Luis
L
Blay
Mayte
M
D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation / Q000517:prevention & control; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D044945:Proanthocyanidins / Q000494:pharmacology*; D012639:Seeds / Q000737:chemistry*; D014280:Triglycerides / Q000378:metabolism; D027843:Vitis / Q000737:chemistry*
D008077:Lipoproteins, LDL; D044945:Proanthocyanidins; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D002784:Cholesterol