title: Brain microvascular and intracranial artery resistance to atherosclerosis is associated with heme oxygenase and ferritin in Japanese quail.
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.
authors.affiliation: Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. khoekstra@wschiro.edu
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Hoekstra
authors.forename: Sandra G
authors.initials: SG
authors.lastname: Velleman
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000494:pharmacology; D003370:Coturnix; D004789:Enzyme Activation / Q000187:drug effects; D005293:Ferritins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D002537:Intracranial Arteriosclerosis / Q000235:genetics* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D018384:Oxidative Stress / Q000502:physiology; D013997:Time Factors
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D005293:Ferritins; D002784:Cholesterol; D051547:Heme Oxygenase-1