Skip to main content
Article thumbnail
Location of Repository

Internal mammary artery smooth muscle cells resist migration and possess high antioxidant capacity

By Vaikom Mahadevan, Malcolm Campbell, Pascal McKeown and Ulvi Bayraktutan


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 �g/ml) nor native LDL (100 �g/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 �M), and MnTBAP (a free radical scavenger, 50��M). 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

Publisher: Elsevier
Year: 2006
OAI identifier:
Provided by: Nottingham ePrints

Suggested articles


  1. (1995). A rapid method for measurement of the susceptibility to oxidation of low-density-lipoprotein.
  2. (1997). Analyzing chemotaxis using the Dunn direct-viewing chamber.
  3. (1990). Automated assays for superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activity.
  4. Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity.
  5. (1994). Cellular defenses against damage from reactive oxygen species. Physiol Rev
  6. (2000). Effects of valsartan on angiotensin II-induced migration of human coronary artery smooth muscle cells. Hypertension Res
  7. Evidence for the presence of oxidatively modified LDL in atherosclerotic lesions of rabbit and man.
  8. Free radicals, diabetes and endothelial dysfunction.
  9. Glucose-induced phosphatidylinositol 3-kinase and mitogen-activated protein kinase-dependent upregulation of the platelet-derived growth factor-beta receptor potentiates vascular smooth muscle cell chemotaxis.
  10. Glucosepotentiated chemotaxis in human vascular smooth muscle is dependent on cross-talk between the PI3K and MAPK signaling pathways.
  11. (1998). Glutathione-related antioxidant defenses in human atherosclerotic plaques. Circulation
  12. HMG-CoA reductase inhibitors prevent migration of human coronary smooth muscle cells through suppression of increase in oxidative stress.
  13. Impaired activities of antioxidant enzymes elicit endothelial dysfunction in SHR, despite enhanced vascular nitric oxide generation.
  14. (2000). Improvement of nitric oxide-dependent vasodilatation by HMG-CoA reductase inhibitors through attenuation of endothelial superoxide anion formation. Arterioscler Thromb Vasc Biol doi
  15. In vitro knockout of human p47-phox blocks superoxide anion production and LDL oxidation by human monocytes.
  16. (1999). Intracranial arteries of human fetuses are more resistant to hypercholesterolemiainduced fatty streak formation than extracranial arteries. Circulation
  17. Modification of PI3K- and MAPK-dependent chemotaxis in aortic vascular smooth muscle cells by protein kinase CII.
  18. NAD(P)H oxidase: role in cardiovascular biology and disease.
  19. (1996). NativeLDL increases endothelial cell adhesiveness by inducing intracellular adhesion molecule-1. Arterioscler Thromb Vasc Biol
  20. (1995). Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia.
  21. Reactive oxygen species and ERK 1/2 mediate monocyte chemotactic protein-1-stimulated smooth muscle cell migration.
  22. Rho GTPases and the actin cytoskeleton. Science 1998;279:509-14. Legends doi
  23. (1993). Simvastatin inhibits PDGFinduced DNA synthesis in human glomerular mesangial cells.
  24. (1999). Sterols and isoprenoids: signalling molecules derived from the cholesterol biosynthetic pathway. Annu Rev Biochem
  25. Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor.
  26. (1994). Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet
  27. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril on cardiovascular events in high risk patients.
  28. (1993). The pathogenesis of atherosclerosis: a perspective for the 1990s.
  29. (1992). The simultaneous generation of superoxide and nitric oxide can initiate lipid peroxidation in human low-density-lipoprotein. Free Radic Res
  30. (1995). The use of the internal mammary artery for revascularization of the left anterior descending artery.
  31. (1997). Upregulation of vascular angiotensin II receptor gene expression by LDL in vascular smooth muscle cells. Circulation
  32. (1994). Vascular renin-angiotensin-system, endothelial function and atherosclerosis? Basic Res Cardiol

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.