The effects of diet and lovastatin on regression of fatty streak lesions and on hepatic and intestinal mRNA levels for the LDL receptor and HMG CoA reductase in F1B hamsters.
This study examined the effects of lovastatin supplementation (25 mg/kg per day) in conjunction with an atherogenic diet (10% coconut oil (w/w), 0.05% cholesterol) on regression of pre-existing foam cells and on hepatic and intestinal LDL receptor and HMG CoA reductase mRNA levels. F1B hamsters fed the atherogenic diet had significantly greater (p < 0.0002) foam cell accumulation (10078 +/- 1452 (S.E.M.) micron2) compared to those fed a low fat, no cholesterol chow diet (64 +/- 10 micron2) or the atherogenic diet supplemented with lovastatin (1621 +/- 132 micron2). Regression of fatty streak lesions was achieved by feeding either a chow diet or supplementing the atherogenic diet with lovastatin as evidenced by the significant (p < 0.0002) reduction in foam cell accumulation in the chow regression (94 +/- 55 micron2) and lovastatin regression (48 +/- 18 micron2) groups compared to the atherogenic diet group (10078 +/- 1452 micron2). Lovastatin supplementation of the atherogenic diet induced significant upregulation of both LDL receptor and HMG CoA reductase message levels in liver and intestine compared to the chow and atherogenic diet fed groups. These data demonstrate that lovastatin supplementation of an atherogenic diet decreases foam cell accumulation and induces upregulation of hepatic and intestinal LDL receptor and HMG CoA reductase mRNA levels. Furthermore, regression of pre-existing, diet-induced fatty streak lesions can be achieved by lovastatin supplementation of an atherogenic diet or by feeding a low fat, low cholesterol chow diet. The specific effects of lovastatin on foam cell accumulation and regression and messenger RNA levels are secondary to reductions in plasma total cholesterol concentrations and do not demonstrate a direct effect of lovastatin on atherosclerotic lesions.
Pitman
W A
WA
Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
Osgood
D P
DP
Smith
D
D
Schaefer
E J
EJ
Ordovas
J M
JM
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology*; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000494:pharmacology; D006224:Cricetinae; D004032:Diet; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics*
D002791:Cholesterol, Dietary; D004041:Dietary Fats; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D011973:Receptors, LDL; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases