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Low Density Lipoproteins Modulate Collagen Metabolism in Fibroblasts

Department of Internal Medicine, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas

Subramanian Ranganathan, PhD

Department of Physiology, and Biophysics, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas

Jawahar L. Mehta, MD, PhD

Department of Internal Medicine, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas; Department of Physiology, and Biophysics, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas

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.

Key Words: low-density lipoprotein • fibroblasts • collagen • metalloproteinases • atherosclerosis • cardiac remodeling

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 8, No. 2, 161-166 (2003)
DOI: 10.1177/107424840300800209


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