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

Mahadevan, Vaikom, Campbell, Malcolm, McKeown, Pascal and Bayraktutan, Ulvi (2006) Internal mammary artery smooth muscle cells resist migration and possess high antioxidant capacity. Cardiovascular Research, 72 . pp. 60-68.

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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.

Item Type: Article
Keywords: Atherosclerosis, Arteries, Oxygen radicals, Nitric oxide
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Medical Sciences and Graduate Entry Medicine
Depositing User: Sayers, Hazel
Date Deposited: 19 Feb 2007
Last Modified: 04 May 2020 20:30

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