title: Internal mammary artery smooth muscle cells resist migration and possess high antioxidant capacity.
abstract: OBJECTIVE
  This study investigated whether differences exist in atherogen-induced migratory behaviors and basal antioxidant enzyme capacity of vascular smooth muscle cells (VSMC) from human coronary (CA) and internal mammary (IMA) arteries.
  
  
  METHODS
  Migration experiments were performed using the Dunn chemotaxis chamber. The prooxidant [NAD(P)H oxidase] and antioxidant [NOS, superoxide dismutase, catalase and glutathione peroxidase] enzyme activities were determined by specific assays.
  
  
  RESULTS
  Chemotaxis experiments revealed that while both sets of VSMC migrated towards platelet-derived growth factor-BB (1-50 ng/ml) and angiotensin II (1-50 nM), neither oxidized-LDL (ox-LDL, 25-100 microg/ml) nor native LDL (100 microg/ml) affected chemotaxis in IMA VSMC. However, high dose ox-LDL produced significant chemotaxis in CA VSMC that was inhibited by pravastatin (100 nM), mevastatin (10 nM), losartan (10 nM), enalapril (1 microM), and MnTBAP (a free radical scavenger, 50 microM). Microinjection experiments with isoprenoids i.e. geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) showed distinct involvement of small GTPases in atherogen-induced VSMC migration. Significant increases in antioxidant enzyme activities and nitrite production along with marked decreases in NAD(P)H oxidase activity and O2- levels were determined in IMA versus CA VSMC.
  
  
  CONCLUSIONS
  Enhanced intrinsic antioxidant capacity may confer on IMA VSMC resistance to migration against atherogenic agents. Drugs that regulate ox-LDL or angiotensin II levels also exert antimigratory effects.
authors.affiliation: Division of Medicine and Therapeutics, Institute of Clinical Science, Queen's University Belfast, UK.
authors.forename: Vaikom S
authors.initials: VS
authors.lastname: Mahadevan
authors.forename: Malcolm
authors.initials: M
authors.lastname: Campbell
authors.forename: Pascal P
authors.initials: PP
authors.lastname: McKeown
authors.forename: Ulvi
authors.initials: U
authors.lastname: Bayraktutan
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D002633:Chemotaxis; D003331:Coronary Vessels / Q000166:cytology; D004656:Enalapril / Q000494:pharmacology; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008323:Mammary Arteries / Q000166:cytology*; D008665:Metalloporphyrins / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress; D017035:Pravastatin / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D051131:Receptors, Oxidized LDL / Q000378:metabolism; D054460:rho-Associated Kinases
chemical_list: D000577:Amides; D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D016166:Free Radical Scavengers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D008665:Metalloporphyrins; D011725:Pyridines; D051131:Receptors, Oxidized LDL; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; C099252:oxidized low density lipoprotein; C108830:Y 27632; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D004656:Enalapril; D051231:Farnesyltranstransferase; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D019808:Losartan; D017035:Pravastatin