Oxidized low-density lipoprotein increases endothelial intracellular calcium and alters cytoskeletal f-actin distribution.
Central to the pathogenesis of atherosclerosis is an abnormally functioning endothelium and a consequent loss of vascular integrity. These abnormalities may be induced by haemodynamic factors, biochemical substances, and also by oxidatively modified low-density lipoprotein (LDL). To understand the mechanism by which oxidized LDL causes endothelial dysfunction, human umbilical vein endothelial cells (HUVECs) were loaded with FURA-2, and intracellular calcium mobilization was studied in acute (seconds after LDL was injected) or chronic (24 h after LDL was injected) preparations. Our results demonstrate that 100 microg mL(-1) oxidized LDL increases HUVEC intracellular calcium. In contrast, native LDL at this same concentration had no effect. In addition, chronic exposure (24 h) of HUVECs to oxidized LDL significantly increases HUVEC intracellular calcium. Fluorescent photomicrographs of HUVECs stained with BODIPY-phalloidin f-actin indicates that oxidized LDL causes a reorganization of microfilaments. The results of this study demonstrate that the mechanism by which oxidized LDL causes a loss of vascular integrity could be through activation of endothelial cells to increase cytosolic calcium, which alters the endothelial barrier by reorganizing the cytoskeleton.
Zhao
B
B
Platelet Research Unit, Institute of Anatomy, University of Munster, Germany.
Ehringer
W D
WD
Dierichs
R
R
Miller
F N
FN
D000199:Actins / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000009:adverse effects* / Q000502:physiology*; D010084:Oxidation-Reduction; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects
D000199:Actins; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D002118:Calcium