Differential PDGF secretion by graft and aortic SMC in response to oxidized LDL.
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 microg/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/microg DNA and aortic SMC from 21 +/- 1 to 40 +/- 2 pg PDGF/microg DNA. Native LDL had no effect. N-acetylcysteine inhibited oxLDL-induced PDGF increase. Both superoxide and H(2)O(2) 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.
Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
Afaf
A
Absood
Akira
A
Furutani
Tsutomu
T
Kawamura
Linda M
LM
Graham
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D001807:Blood Vessel Prosthesis; D002470:Cell Survival; D004285:Dogs; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011093:Polyethylene Terephthalates; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D008077:Lipoproteins, LDL; D010982:Platelet-Derived Growth Factor; D011093:Polyethylene Terephthalates; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; C075278:platelet-derived growth factor A