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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:328.)
© 2000 American Heart Association, Inc.

Vascular Biology

Lesions in Ryanodine Channels in Smooth Muscle Cells Exposed to Oxidized Low Density Lipoprotein

Hamid Massaeli; J. Alejandro Austria; Grant N. Pierce

From the Division of Stroke and Vascular Disease, St. Boniface General Hospital Research Centre, and the Department of Physiology, University of Manitoba, Winnipeg, Canada.

Correspondence to Dr Grant N. Pierce, Director, Division of Stroke and Vascular Disease, St. Boniface General Hospital Research Centre, 351 Tache Ave, Winnipeg, Manitoba, Canada R2H 2A6. E-mail gpierce{at}sbrc.umanitoba.ca

Abstract—The purpose of the present investigation was to investigate the subcellular basis responsible for the loss of vasoreactivity in atherosclerotic vessels. We have chosen to focus on the potential of oxidized low density lipoprotein (oxLDL), an important atherogenic agent, to alter sarcoplasmic reticulum (SR) structure and function. Vascular smooth muscle cells (VSMCs) were exposed for 1 to 6 days to low concentrations of minimally oxidized LDL. ATP was used to probe SR function in VSMCs. ATP can increase [Ca²⁺]_i in control VSMCs because of a release of Ca²⁺ from the SR. However, after chronic exposure to oxLDL, cells lose their ability to increase [Ca²⁺]_i in response to ATP. These cells also exhibit a depressed rise in [Ca²⁺]_i after exposure to ryanodine. These effects were associated with a decreased immunoreactivity for the ryanodine-sensitive Ca²⁺-release channels in the SR of oxLDL-treated cells. Immunohistochemical analysis of aortic sections obtained from rabbits fed a cholesterol-supplemented diet revealed a significant decrease in the immunoreactivity for ryanodine channels in the plaque and in the medial layer underlying the plaque. In summary, our data identify oxLDL as a component within the atherosclerotic milieu capable of inducing a decrease in smooth muscle ryanodine channel density. This alteration is associated with a significant defect in the ability of the SR within the smooth muscle cell to regulate Ca²⁺. These lesions may contribute to the altered vasoreactivity exhibited by atherosclerotic vessels.

Key Words: Ca²⁺ • atherosclerosis • sarcoplasmic reticulum

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