Nifedipine prevents apoptosis of endothelial cells induced by oxidized low-density lipoproteins.
Calcium channel blockade has been shown to inhibit experimental atherosclerosis, and early clinical trials suggest that it also reduces atherosclerosis in humans. However, the mechanisms underlying the direct protective effect of calcium channel blockade on endothelial cell injury are not fully understood. The apoptosis of endothelial cells induced by oxidized low-density lipoproteins (oxLDL) may provide a mechanistic clue to the "response-to-injury" hypothesis of atherogenesis. Here we report that the calcium channel blocker, nifedipine, prevents the apoptosis of human umbilical venous endothelial cells (HUVECs) induced by oxLDL via downregulation of the endothelial receptor for oxidized LDL (LOX-1) and inhibition of CPP32-like protease activity. The incubation of HUVEC with oxLDL increased LOX-1 mRNA levels and CPP32-like protease activity, and induced apoptosis. Preincubation of HUVEC with nifedipine before incubation with oxLDL significantly suppressed the increase in LOX-1 mRNA levels and CPP32-like protease activity, preventing apoptosis in a dose-dependent manner. These results suggest that nifedipine blocks the suicide pathway leading to the apoptosis of endothelial cells by decreasing LOX-1 mRNA levels and CPP32-like protease activity. Thus, nifedipine seems to play a protective role against the "response-to-injury" hypothesis of atherogenesis.
Sugano
Masahiro
M
Department of Molecular and Cellular Biology, Division of Molecular and Clinical Gerontology, Medical Institute of Bioregulation, Kyushu University, Oita, Japan. massy@tsurumi.beppu.kyushu-u.ac.jp
Tsuchida
Keiko
K
Makino
Naoki
N
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology*; D010084:Oxidation-Reduction
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D009543:Nifedipine