Low density lipoproteins modulate collagen metabolism in fibroblasts.
High levels of low-density lipoprotein are associated with atherosclerosis, and myocardial and arterial remodeling. We postulated that low-density lipoprotein influences collagen synthesis and degradation in fibroblasts as a potential mechanism of tissue remodeling. Incubation of cultured human skin fibroblasts with low-density lipoproteins resulted in a time-dependent and dose-dependent increase in the secretion of matrix metalloproteinase activity measured by gelatin zymography. Western blot analysis showed a concomitant increase in matrix metalloproteinase-1 protein. Northern blot analysis demonstrated an increase in collagen I messenger RNA after treatment with low-density lipoprotein. The matrix metalloproteinase-1 secretory response of fibroblasts to low-density lipoprotein was attenuated by heparin, which inhibits low-density lipoprotein uptake through the low-density lipoprotein-receptor. These observations suggest that low-density lipoprotein has a regulatory effect on collagen metabolism in fibroblasts.
Joseph
Jacob
J
Department of Internal Medicine, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205, USA. josephjacob@uams.edu
Ranganathan
Subramanian
S
Mehta
Jawahar L
JL
D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000187:drug effects / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism
D024042:Collagen Type I; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D011973:Receptors, LDL; D006493:Heparin; D020781:Matrix Metalloproteinase 1