1999 Fiscal Year Annual Research Report

レクチン様酸化LDL受容体の機能と病態生理的役割

Research Project

Project/Area Number	11158224
Research Institution	National Cardiovascular Center Research Institute
Principal Investigator	沢村達也国立循環器病センター研究所, バイオサイエンス部, 室長 (30243033)
Co-Investigator(Kenkyū-buntansha)	眞崎知生国立循環器病センター研究所, バイオサイエンス部, 所長 (60009991)
Keywords	レクチン様酸化LDL受容体 / 酸化LDL / 血小板 / 動脈硬化 / 内皮細胞
Research Abstract	LOX-1の発現調節について検討を加えた。リガンドである酸化LDLそのものによってLOX-1の発現は増強され、実際、動脈硬化巣内のように酸化LDLが蓄積しているような部位ではLOX-1の発現が亢進していることを確認した。またヒトにおいてはアンジオテンシン変換酵素阻害薬により発現が抑制されることも見いだしている。一方、LOX-1の発現は培養マクロファージや平滑筋でも確認され、in vivoにおいては進んだ動脈硬化巣でマクロファージや平滑筋に発現が見られることを示した。従ってLOX-1は平滑筋やマクロファージでも機能し、泡沫細胞の形成をはじめとする酸化LDLの種々の作用を媒介している可能性が示唆された。 LOX-1はフォスファチジルセリンをリガンドとしてアポトーシス細胞を認識することを見いだしていた。これを手がかりに、活性化した血小板の認識にもLOX-1が重要であることを本研究で明らかにしている。さらに、ヒトLOX-1の遺伝子が6つのエクソンからなり、12番染色体の短腕に位置することを明らかにした。LOX-1がホモロジーを持つNK cell receptor familyの遺伝子構造および遺伝子座と、LOX-1のエクソンの構成および遺伝子の位置は共に一致しており、両者が共通の遺伝子から進化の過程で枝分かれしてきたことが示唆された。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Li, D.Y., Zhang, Y.C.: "Upregulation of endothelial receptor for oxidized low-density lipoprotein (LOX-1) in cultured human coronary artery endothelial cells by angiotensin II type 1 receptor activation"Circ Res. 84. 1043-1049 (1999)
[Publications] Aoyama, T.: "Structure and chromosomal assignment of the human lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) gene"Biochem J. 339. 177-184 (1999)
[Publications] Kataoka, H.: "Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions"Circulation. 99. 3110-3117 (1999)
[Publications] Masaki, T.: "Subcellular mechanisms of endothelin action in vascular system"Eur J Pharmacol. 375. 133-138 (1999)
[Publications] Kaburagi, S.: "The role of endothelin-converting enzyme-1 in the development of alpha1-adrenergic-stimulated hypertrophy in cultured neonatal rat cardiac myocytes"Circulation. 99. 292-298 (1999)
[Publications] Morawietz, H.: "Angiotensin II induces LOX-1, the human endothelial receptor for oxidized low-density lipoprotein"Circulation. 100. 899-902 (1999)
[Publications] Hosokawa, H.: "Neuron-specific expression of cationic amino acid transporter 3 in the adult rat brain"Brain Res. 838. 158-165 (1999)
[Publications] Aoyama, T.: "Induction of lectin-like oxidized LDL receptor by oxidized LDL and lysophosphatidylcholine in cultured endothelial cells [In Process Citation]"J Mol Cell Cardiol 31. 31. 2101-2114 (1999)
[Publications] Aoyama, T.: "LOX-1 mediates lysophosphatidylcholine-induced oxidized LDL uptake in smooth muscle cells"FEBS letters. 467. 217-220 (2000)
[Publications] Kakutani, M.: "A platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1"Proc Natl Acad Sci USA. 97. 360-364 (2000)
[Publications] Chen, M.: "Increased expression of lectin-like oxidized low density lipoprotein receptor-1 in initial atherosclerotic lesions of Watanabe heritabie hyperlipidemic rabbits"Arterioscler. Thromb. Vasc. Biol. (in press). (2000)
[Publications] Cominacini, L.: "Oxidized Low-density lipoprotein binding to LOX-1 in endothelial cells induces the activation of NF-kB through an increased production of intracellular reactive oxygen species"J. Biol. Chem. (in press). (2000)

1999 Fiscal Year Annual Research Report

レクチン様酸化LDL受容体の機能と病態生理的役割

Principal Investigator

沢村 達也 国立循環器病センター研究所, バイオサイエンス部, 室長 (30243033)

Research Products

[Publications] Li, D.Y., Zhang, Y.C.: "Upregulation of endothelial receptor for oxidized low-density lipoprotein (LOX-1) in cultured human coronary artery endothelial cells by angiotensin II type 1 receptor activation"Circ Res. 84. 1043-1049 (1999)

[Publications] Aoyama, T.: "Structure and chromosomal assignment of the human lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) gene"Biochem J. 339. 177-184 (1999)

[Publications] Kataoka, H.: "Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions"Circulation. 99. 3110-3117 (1999)

[Publications] Masaki, T.: "Subcellular mechanisms of endothelin action in vascular system"Eur J Pharmacol. 375. 133-138 (1999)

[Publications] Kaburagi, S.: "The role of endothelin-converting enzyme-1 in the development of alpha1-adrenergic-stimulated hypertrophy in cultured neonatal rat cardiac myocytes"Circulation. 99. 292-298 (1999)

[Publications] Morawietz, H.: "Angiotensin II induces LOX-1, the human endothelial receptor for oxidized low-density lipoprotein"Circulation. 100. 899-902 (1999)

[Publications] Hosokawa, H.: "Neuron-specific expression of cationic amino acid transporter 3 in the adult rat brain"Brain Res. 838. 158-165 (1999)

[Publications] Aoyama, T.: "Induction of lectin-like oxidized LDL receptor by oxidized LDL and lysophosphatidylcholine in cultured endothelial cells [In Process Citation]"J Mol Cell Cardiol 31. 31. 2101-2114 (1999)

[Publications] Aoyama, T.: "LOX-1 mediates lysophosphatidylcholine-induced oxidized LDL uptake in smooth muscle cells"FEBS letters. 467. 217-220 (2000)

[Publications] Kakutani, M.: "A platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1"Proc Natl Acad Sci USA. 97. 360-364 (2000)

[Publications] Chen, M.: "Increased expression of lectin-like oxidized low density lipoprotein receptor-1 in initial atherosclerotic lesions of Watanabe heritabie hyperlipidemic rabbits"Arterioscler. Thromb. Vasc. Biol. (in press). (2000)

[Publications] Cominacini, L.: "Oxidized Low-density lipoprotein binding to LOX-1 in endothelial cells induces the activation of NF-kB through an increased production of intracellular reactive oxygen species"J. Biol. Chem. (in press). (2000)

沢村達也国立循環器病センター研究所, バイオサイエンス部, 室長 (30243033)