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Brain microvascular and intracranial artery resistance to atherosclerosis is associated with heme oxygenase and ferritin in Japanese quail

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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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Abbreviations

CIA:

Cholesterol-induced atherosclerosis

HO:

Heme oxygenase

QAEC:

Quail aortic endothelial cells

QBMEC:

Quail brain microvascular endothelial cells

EC:

Endothelial cells

oxLDL:

Oxidized low-density lipoprotein

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Acknowledgments

The authors would like to thank the technical staff at the Pulmonary Research Centre, St. Pauls Hospital, Vancouver, BC, Canada and Cindy Coy at Ohio State University for technical assistance. Special thanks to Prof. Carollo and Dr. B. Boal for their critical review. The quail endothelial cell antibody (QH1) was a gift from Dr. C.A. Buck, The Wistar Institute, Philadelphia, PA, USA. The quail smooth muscle antibody (1E12) was a gift from Dr. C.D. Little, Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, USA. Research support to SGV was provided by state and federal funds appropriated to the Ohio Agricultural Research and Development Center, The Ohio State University.

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Authors and Affiliations

  1. Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada, V6T 2B5

    Kenneth A. Hoekstra

  2. Division of Basic Sciences, Western States Chiropractic College, 2900 NE 132nd avenue, Portland, OR, 97230, USA

    Kenneth A. Hoekstra

  3. Department of Animal Sciences, Ohio State University, Wooster, OH, 44691, USA

    Sandra G. Velleman

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Correspondence to Kenneth A. Hoekstra.

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Hoekstra, K.A., Velleman, S.G. Brain microvascular and intracranial artery resistance to atherosclerosis is associated with heme oxygenase and ferritin in Japanese quail. Mol Cell Biochem 307, 1–12 (2008). https://doi.org/10.1007/s11010-007-9577-4

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