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

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

Authors

Vaikom Mahadevan

Malcolm Campbell

Pascal McKeown



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

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