Submitted on March 8, 2004
Accepted on May 11, 2004
A Comparison of Oxidized LDL-induced Collagen Secretion by Graft and Aortic SMC: Role of PDGF
Afaf Absood1, Akira Furutani2, Tsutomu Kawamura3, and Linda M. Graham3*
1 Department of Surgery, University of Michigan and Department of Veternas Affairs Medical Center, Ann Arbor, MI, USA
2 First Department of Surgery, Yamaguchi University School of Medicine, Ube, Yamaguchi, JAPAN
3 Department of Biomedical Engineering and 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 constitutively secrete higher levels of collagen than aortic SMC. 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 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 cholesterol/ml) for 72 h. Type I collagen in the conditioned medium was measured by enzyme-linked immunosorbent assay (ELISA). OxLDL increased collagen production by graft SMC from 4.1±0.3 to 11.0±0.4 ng/µg DNA and by aortic SMC from 2.3±0.1 to 3.5±0.2 ng/µg DNA. Native LDL had little effect. LY83583, a superoxide generator, stimulated a dramatic increase in collagen secretion by graft SMC, and a smaller but significant elevation in aortic SMC. OxLDL has been shown to increase platelet-derived growth factor (PDGF) production by graft SMC, and PDGF can stimulate collagen
production. Anti-PDGF antibody inhibited the increase in collagen production by graft SMC that was stimulated by oxLDL, implicating PDGF as one mechanism for oxLDL-induced collagen production. Lipid oxidation products that accumulate in prosthetic vascular grafts can cause an oxidative stress that stimulates PDGF production by graft SMC that in turn stimulates collagen production, contributing to the progression of intimal hyperplasia.
