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

Mahadevan, Vaikom; Campbell, Malcolm; McKeown, Pascal; Bayraktutan, Ulvi

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 �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.

Citation

Mahadevan, V., Campbell, M., McKeown, P., & Bayraktutan, U. (2006). Internal mammary artery smooth muscle cells resist migration and possess high antioxidant capacity. Cardiovascular Research, 72,

• Journal Article Type: Article
• Publication Date: Jan 1, 2006
• Deposit Date: Feb 19, 2007
• Publicly Available Date: Oct 9, 2007
• Journal: Cardiovascular Research
• Print ISSN: 0008-6363
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 72
• Keywords: Atherosclerosis, Arteries, Oxygen radicals, Nitric oxide
• Public URL: https://nottingham-repository.worktribe.com/output/1019276