Prostaglandin E1 dose-dependently promotes stability of atherosclerotic plaque in a rabbit model.
This study evaluated the effect of prostaglandin E1 (PGE1) on the stability of atherosclerotic plaque. A vulnerable plaque model was established in rabbits, using balloon injury combined with a high-cholesterol diet. The rabbits were distributed into a control group, a low-dose PGE1 treatment group, a moderate-dose PGE1 treatment group, a high-dose PGE1 treatment group, and a simvastatin treatment group, with treatments lasting for 4 weeks. At week 13 (at the end of the experiments), atherosclerotic plaque was triggered by injection of Russell's viper venom (Chinese) and histamine. Serological, pathological, immunohistochemical, and gene-expression studies were subsequently performed. PGE1 treatment did not alter serum lipid levels; however, PGE1 dose-dependently increased the thickness of the fibrous caps, and decreased the plaque vulnerability index. The plaque contents of macrophage- and the mRNA levels of monocyte-chemotactic protein-1, matrix metalloproteinase-1, and matrix metalloproteinase-9 were markedly reduced in all of the PGE1 treatment groups, with the high-dose of PGE1 being more effective than the simvastatin treatment. These findings suggest that PGE1 dose-dependently enhances the stability of atherosclerotic plaque. The high-dose of PGE1 presented more protection in terms of inhibiting macrophage accumulation and inflammatory expression in plaque. Our findings suggest a novel drug for the treatment of atherosclerosis.
Department of Clinical Pharmacy, School of Pharmacy, Shandong University, Jinan, Shandong 250012, P.R. China.
Wanjun
W
Bai
Xue
X
Zheng
Liaosheng
L
Zhou
Hongjian
H
Li
D000527:Alprostadil / Q000494:pharmacology*; D000800:Angioplasty, Balloon; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D002791:Cholesterol, Dietary; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005355:Fibrosis; D006632:Histamine; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D017840:Daboia; D019821:Simvastatin / Q000494:pharmacology; D014757:Viper Venoms
D000893:Anti-Inflammatory Agents; D002317:Cardiovascular Agents; D018932:Chemokine CCL2; D002791:Cholesterol, Dietary; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D012333:RNA, Messenger; D014757:Viper Venoms; D006632:Histamine; D019821:Simvastatin; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D000527:Alprostadil