Native and minimally oxidized low density lipoprotein depress smooth muscle matrix metalloproteinase levels.
Vascular lesion development is associated with an accumulation of extracellular matrix proteins within the vessel wall. Matrix metalloproteinases (MMPs) degrade these proteins. Conversely, oxidized low density lipoprotein (LDL) is implicated in atherogenesis through, amongst other cellular effects, a stimulation of the deposition of collagen within the vascular lesion. The present study investigated the potential for an interaction between oxidized LDL and MMP levels. Within the vessel wall fibroblasts, smooth muscle, endothelial and infiltrating cells have been reported to secrete MMPs into the extracellular space to effect remodeling of the extracellular matrix. A consequence of angioplasty and atherosclerotic disease is the loss of endothelial cells or endothelial function, respectively. We have investigated the effects of chronic incubation of cultured vascular smooth muscle cells from rabbit thoracic aorta with oxidized LDL and its influence on MMP levels in the extracellular space. Our data indicate that a low concentration of minimally oxidized LDL (0.005 mg/mL) significantly depressed the levels of MMP-2 and MMP-9 present in the culture medium. Native LDL exerted the same effect but exhibited reduced potency. The effects were not attributable to cytotoxicity exerted by the oxidized LDL. The reduction in MMP secretion into the extracellular medium was a result of decreased enzyme synthesis within the smooth muscle cell. Our results demonstrate that an important atherogenic moiety, oxidized LDL, can reduce MMP activity and hence has the potential to increase the deposition of extracellular matrix proteins within SMC-rich vascular lesions.
Wilson
David
D
Institute of Cardiovascular Sciences, Winnipeg, Manitoba, Canada.
Massaeli
Hamid
H
Pierce
Grant N
GN
Zahradka
Peter
P
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology; D005109:Extracellular Matrix / Q000201:enzymology; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D011817:Rabbits
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9