Brain microvascular and intracranial artery resistance to atherosclerosis is associated with heme oxygenase and ferritin in Japanese quail |
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Authors: | Kenneth A Hoekstra Sandra G Velleman |
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Institution: | (1) Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada, V6T 2B5;(2) Division of Basic Sciences, Western States Chiropractic College, 2900 NE 132nd avenue, Portland, OR 97230, USA;(3) Department of Animal Sciences, Ohio State University, Wooster, OH 44691, USA |
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Abstract: | Oxidative stress and increased oxidation of low-density lipoprotein (oxLDL) through free radical-mediated tissue injury may
be important factors in the development of extracranial atherosclerotic lesions. However, the roles of oxidative stress and
hypercholesterolemia in intracranial atherosclerosis is less established. The induction of heme oxygenase (HO) is a cellular
response to oxidative stress, and inducible HO (HO-1) may protect against oxidized lipids such as those produced by oxidative
stress. We investigated the effects of oxLDL on cell and tissue viability, HO-1 and ferritin expression in extracranial and
intracranial endothelial cells, and the arteries of cholesterol-induced atherosclerosis (CIA) Japanese quail. We report that
cultured microvascular endothelial cells from the brain (QBMEC) and carotid (QCEC) differ in their response to oxidative stress.
The QCECs are less responsive than QBMECs to oxidative stress induced by oxLDL, as evident by lower expression of HO-1 mRNA,
HO activity, and ferritin levels. Furthermore, the higher levels of catalytic iron, thiobarbituric acid reactive substances,
and lactate dehydrogenase released in QCECs indicated that these cells are more susceptible to oxidative stress than QBMECs.
We also investigated the relationship between extent of atherosclerotic plaque deposition and the extracranial and intracranial
arterial expression of HO-1 in quail. The common carotid and vertebral (extracranial) arteries had higher tissue cholesterol
levels (starting at 2 weeks of cholesterol-supplementation) and a greater atherosclerotic plaque score (starting at 4 weeks
of cholesterol-supplementation) compared with middle cerebral and basilar (intracranial) arteries, and this may be relevant
to the effect of aging on the process of atherogenesis. The extracranial arteries also had early and greater levels of lipid
peroxidation and catalytic iron coupled with lower expression of HO-1 protein, HO activity, and ferritin compared to the intracranial
vessels. These observations suggest that the extracranial and intracranial arterial walls respond differently to oxidation
of lipoproteins, and support the feasibility of increased HO-1 expression as a means of protection against oxidant injury. |
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Keywords: | Oxidative stress Antioxidant Heme oxygenase Ferritin Catalytic iron Intracranial Extracranial |
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