Overexpression of SERCA2 ATPaase in vascular smooth muscle cells treated with oxidized low density lipoprotein

Oxidized low density lipoprotein (oxLDL) has been identified as a potential ly important atherogenic factor. Atherosclerosis is characterized by the ac cumulation of lipid and calcium in the vascular wall. OxLDL plays a signifi cant role in altering calcium homeostasis within different cell types. In o ur previous study, chronic treatment of vascular smooth muscle cells (VSMC) with oxLDL depressed Ca-i(2+) homeostasis and altered two Ca2+ release mec hanisms in these cells (IP3 and ryanodine sensitive channels). The purpose of the present study was to further define the effects of chronic treatment with oxLDL on the smooth muscle sarcoplasmic reticulum (SR) Ca2+ pump. One of the primary Ca2+ uptake mechanisms in VSMC is through the SERCA2 ATPase calcium pump in the sarcoplasmic reticulum. VSMC were chronically treated with 0.005-0.1 mg/ml oxLDL for up to 6 days in culture. Cells treated with oxLDL showed a significant increase in the total SERCA2 ATPase content. The se changes were observed on both Western blot and immunocytochemical analys is. This increase in SERCA2 ATPase is in striking contrast to a significant decrease in the density of IP3 and ryanodine receptors in VSMC as the resu lt of chronic treatment with oxLDL. This response may suggest a specific ad aptive mechanism that the pump undergoes to attempt to maintain Ca2+ homeos tasis in VSMC chronically exposed to atherogenic oxLDL.