Lesions in ryanodine channels in smooth muscle cells exposed to oxidized low density lipoprotein

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

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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.

Original languageEnglish
Pages (from-to)328-334
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number2
Publication statusPublished - 1 Jan 2000
Externally publishedYes



  • Atherosclerosis
  • Ca
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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