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Am J Physiol Heart Circ Physiol (April 11, 2002). doi:10.1152/ajpheart.00060.2002
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Articles in PresS, published online ahead of print April 11, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00060.2002
Submitted on January 23, 2002
Accepted on April 9, 2002

DIFFERENTIAL PDGF SECRETION BY GRAFT AND AORTIC SMC IN RESPONSE TO OXIDIZED LDL

Afaf Absood1, Akira Furutani2, Tsutomu Kawamura3, and Linda M. Graham4*

1 Surgery, University of Michigan, Ann Arbor, MI, USA; Surgery, Department of Veterans Affairs, Ann Arbor, MI, USA
2 Surgery, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
3 Biomedical Engineering, Cleveland Clinic Foundation, Cleveland, OH, USA
4 Biomedical Engineering, Cleveland Clinic Foundation, Cleveland, OH, USA; Vascular Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA

* To whom correspondence should be addressed. E-mail: grahaml{at}ccf.org.

Smooth muscle cells (SMC) from prosthetic vascular grafts 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. SMC isolated from canine thoracic aorta or Dacron thoracoabdominal grafts (n=10) were incubated with native low density lipoprotein (LDL) or oxidized LDL (oxLDL) for 72 h, and secreted PDGF-AA measured by ELISA. 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. Graft (synthetic) SMC were also stimulated to produce increased PDGF by other reactive oxygen species which had little effect on aortic SMC. Lipid oxidation products which accumulate in grafts can cause an oxidative stress which stimulates PDGF production by graft SMC. The PDGF can induce migration of aortic SMC onto the graft, contributing to the development of intimal hyperplasia.




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