Antioxidant vitamins increase the collagen content and reduce MMP-1 in a porcine model of atherosclerosis: implications for plaque stabilization.
Degradation of extracellular matrix, particularly interstitial collagen, promotes plaque instability and contributes to restenosis after vascular injury. We have explored the effects of vitamins C and E on the collagen content and metalloproteinase-1 (MMP-1) expression after angioplasty in hypercholesterolemic pigs. Iliac angioplasty was performed on 18 minipigs divided into three diet groups: a normal-cholesterol (NC), a high-cholesterol (HC) and a high-cholesterol plus vitamins C+E (HCV). Four weeks later, after sacrifice, the vascular collagen content and MMP-1 protein expression, along with the plasma caseinolytic activity and lipid peroxidation, were measured. MMP-1 was also determined in arterial rings stimulated with native low-density lipoproteins (LDL) isolated from experimental groups. Cholesterol-rich diet augmented plasma lipid peroxidation (P<0.05), reduced the collagen content and increased vascular MMP-1 expression after injury (P<0.05). Enhanced caseinolytic activity (identified as MMP-1) was also observed in HC plasma samples and in supernatants from arterial rings incubated with HC-LDL. Vitamins C and E markedly increased neointimal collagen content (P<0.01), reduced the hypercholesterolemia-induced changes in vascular MMP-1 (P<0.05) and diminished plasma and ex vivo caseinolytic activity. Vitamins C and E may help stabilize atherosclerotic plaque after angioplasty and favor vascular remodeling by increasing collagen content and reducing vascular MMP-1 expression in porcine hypercholesterolemia.
Orbe
J
J
Atherosclerosis Research Laboratory, Division of Cardiovascular Pathophysiology, School of Medicine, University of Navarra, C/Irunlarrea 1, CIFA, E-31008 Pamplona, Spain.
Rodríguez
J A
JA
Arias
R
R
Belzunce
M
M
Nespereira
B
B
Pérez-Ilzarbe
M
M
Roncal
C
C
Páramo
J A
JA
D000704:Analysis of Variance; D017130:Angioplasty / Q000379:methods; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000503:physiopathology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D002791:Cholesterol, Dietary; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000503:physiopathology*; D007083:Iliac Artery / Q000473:pathology* / Q000601:surgery; D015227:Lipid Peroxidation; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D011336:Probability; D012680:Sensitivity and Specificity; D013556:Swine, Miniature; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D002791:Cholesterol, Dietary; D014810:Vitamin E; D002784:Cholesterol; D020781:Matrix Metalloproteinase 1; D001205:Ascorbic Acid