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This Article Full Text Full Text (PDF) All Versions of this Article: 287/3/H1200    most recent 00228.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Absood, A. Articles by Graham, L. M. Search for Related Content PubMed PubMed Citation Articles by Absood, A. Articles by Graham, L. M.

A comparison of oxidized LDL-induced collagen secretion by graft and aortic SMCs: role of PDGF

¹Department of Surgery, University of Michigan and Department of Veterans Affairs Medical Center, Ann Arbor, Michigan 48019; ²First Department of Surgery, Yamaguchi University School of Medicine, Ube, 755-8505 Yamaguchi, Japan; and ³Departments of Biomedical Engineering and Vascular Surgery, Cleveland Clinic Foundation, Cleveland, Ohio 44195

Submitted 8 March 2004 ; accepted in final form 11 May 2004

Smooth muscle cells (SMCs) from prosthetic vascular grafts constitutively secrete higher levels of collagen than aortic SMCs. Lipid oxidation products accumulate in grafts, and we postulated that they stimulate SMC production of collagen. The effect of oxidized low-density lipoprotein (oxLDL) on type I collagen secretion by aortic and graft SMCs was compared. SMCs isolated from the canine thoracic aorta or Dacron thoracoabdominal grafts (n = 10) were incubated with native LDL or oxLDL (0–400 µg cholesterol/ml) for 72 h. Type I collagen in the conditioned medium was measured by ELISA. OxLDL increased collagen production by graft SMCs from 4.1 ± 0.3 to 11.0 ± 0.4 ng/µg DNA and by aortic SMCs from 2.3 ± 0.1 to 3.5 ± 0.2 ng/µg DNA. Native LDL had little effect. LY-83583, a superoxide generator, stimulated a dramatic increase in collagen secretion by graft SMCs and a smaller but significant elevation by aortic SMCs. OxLDL has been shown to increase PDGF production by graft SMCs, and PDGF can stimulate collagen production. Anti-PDGF antibody inhibited the increase in collagen production by graft SMCs that was stimulated by oxLDL, implicating PDGF as one mechanism of oxLDL-induced collagen production. Lipid oxidation products that accumulate in prosthetic vascular grafts can cause an oxidative stress that stimulates PDGF production by graft SMCs that in turn stimulates collagen production, contributing to the progression of intimal hyperplasia.

smooth muscle cell; collagen; low-density lipoprotein; reactive oxygen species; platelet-derived growth factor