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Am J Physiol Heart Circ Physiol 283: H725-H732, 2002. First published April 11, 2002; doi:10.1152/ajpheart.00060.2002
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Vol. 283, Issue 2, H725-H732, August 2002

Differential PDGF secretion by graft and aortic SMC in response to oxidized LDL

Afaf Absood1, Akira Furutani2, Tsutomu Kawamura3, and Linda M. Graham3

1 Department of Surgery, University of Michigan and Department of Veterans Affairs Medical Center, Ann Arbor, Michigan 48109; 2 First Department of Surgery, Yamaguchi University School of Medicine, Ube, 755-8505 Yamaguchi, Japan; and 3 Departments of Biomedical Engineering and Vascular Surgery, Cleveland Clinic Foundation, Cleveland, Ohio 44195

Smooth muscle cells (SMC) from prosthetic vascular grafts constitutively secrete higher levels of platelet-derived growth factor-AA (PDGF-AA) than aortic SMC. Lipid oxidation products accumulate in grafts and may stimulate PDGF production. The effect of oxidized low-density lipoprotein (oxLDL) on PDGF-AA secretion by aortic and graft SMC was compared. SMC isolated from canine thoracic aorta or Dacron thoracoabdominal grafts (n = 10) were incubated with native LDL or oxLDL (0-400 µg/ml) for 72 h. PDGF-AA in the conditioned medium was measured with enzyme-linked immunosorbent assay. OxLDL increased PDGF-AA production by graft SMC from 78 ± 2 to 256 ± 16 pg PDGF/µg DNA and aortic SMC from 21 ± 1 to 40 ± 2 pg PDGF/µg DNA. Native LDL had no effect. N-acetylcysteine inhibited oxLDL-induced PDGF increase. Both superoxide and H2O2 stimulated PDGF secretion by graft SMC had little effect on aortic SMC. Our results suggest that PDGF production by graft (synthetic) SMC is more sensitive to stimulation by oxidative stress than aortic (contractile) SMC. Lipid oxidation products that accumulate in prosthetic vascular grafts can cause an oxidative stress, which stimulates PDGF production by graft SMC. PDGF can induce migration of aortic SMC onto the graft, contributing to the development of intimal hyperplasia.

oxidative stress; reactive oxygen species; mitogen; phenotype; platelet-derived growth factor; smooth muscle cells; low-density lipoprotein


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