Antioxidant vitamins increase the collagen content and reduce MMP-1 in a porcine model of atherosclerosis: implications for plaque stabilization
Orbe J, Rodríguez JA, Arias R, Belzunce M, Nespereira B, Pérez-Ilzarbe M, Roncal C, Páramo JA.
Atherosclerosis Research Laboratory, Division of Cardiovascular Pathophysiology, School of Medicine, University of Navarra, C/Irunlarrea 1, CIFA, E-31008 Pamplona, Spain.
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.
CITATION Atherosclerosis. 2003 Mar;167(1):45-53