TY - JOUR
T1 - Comparative reactivity of remnant-like lipoprotein particles (RLP) and low-density lipoprotein (LDL) to LDL receptor and VLDL receptor
T2 - Effect of a high-dose statin on VLDL receptor expression
AU - Imagawa, Michiko
AU - Takahashi, Sadao
AU - Zenimaru, Yasuo
AU - Kimura, Tomoko
AU - Suzuki, Jinya
AU - Miyamori, Isamu
AU - Iwasaki, Tadao
AU - Hattori, Hiroaki
AU - Yamamoto, Tokuo T.
AU - Nakano, Takamitsu
AU - Nakajima, Katsuyuki
N1 - Funding Information:
We thank Ms. F. Kitaguchi for the excellent technical assistance. This study was supported by research grants from the Ministry of Education, Science and Culture and the Ministry of Health, Labor and Welfare (# 23591335 to S.T.).
PY - 2012/2/18
Y1 - 2012/2/18
N2 - Background: Comparison of the reactivity of remnant-like lipoprotein particles (RLP) and LDL particles to LDL receptor and VLDL receptor has not been investigated. Methods: LDL receptor- or VLDL receptor-transfected ldlA-7, HepG2 and L6 cells were used. Human LDL and rabbit β-VLDL were isolated by ultracentrifugation. Human RLP was isolated using an immunoaffinity mixed gel. The effect of statin on lipoprotein receptors was examined. Results: Both LDL receptor and VLDL receptor recognized RLP. In LDL receptor transfectants, RLP, β-VLDL and LDL all bound to LDL receptor. Cold RLP competed efficiently with DiI-β-VLDL; however, cold LDL competed weakly. In VLDL receptor transfectants, RLP and β-VLDL bound to VLDL receptor, but not LDL. RLP bound to VLDL receptor with higher affinity than β-VLDL because of higher apolipoprotein E in RLP. LDL receptor expression was induced in HepG2 by the low concentration of statin while VLDL receptor expression was induced in L6 myoblasts at higher concentration. Conclusions: RLP are bound to hepatic LDL receptor more efficiently than LDL, which may explain the mechanism by which statins prevent cardiovascular risk by primarily reducing plasma RLP rather than by reducing LDL. Additionally, a high-dose of statins also may reduce plasma RLP through muscular VLDL receptor.
AB - Background: Comparison of the reactivity of remnant-like lipoprotein particles (RLP) and LDL particles to LDL receptor and VLDL receptor has not been investigated. Methods: LDL receptor- or VLDL receptor-transfected ldlA-7, HepG2 and L6 cells were used. Human LDL and rabbit β-VLDL were isolated by ultracentrifugation. Human RLP was isolated using an immunoaffinity mixed gel. The effect of statin on lipoprotein receptors was examined. Results: Both LDL receptor and VLDL receptor recognized RLP. In LDL receptor transfectants, RLP, β-VLDL and LDL all bound to LDL receptor. Cold RLP competed efficiently with DiI-β-VLDL; however, cold LDL competed weakly. In VLDL receptor transfectants, RLP and β-VLDL bound to VLDL receptor, but not LDL. RLP bound to VLDL receptor with higher affinity than β-VLDL because of higher apolipoprotein E in RLP. LDL receptor expression was induced in HepG2 by the low concentration of statin while VLDL receptor expression was induced in L6 myoblasts at higher concentration. Conclusions: RLP are bound to hepatic LDL receptor more efficiently than LDL, which may explain the mechanism by which statins prevent cardiovascular risk by primarily reducing plasma RLP rather than by reducing LDL. Additionally, a high-dose of statins also may reduce plasma RLP through muscular VLDL receptor.
KW - LDL
KW - LDL receptor
KW - RLP
KW - Statins
KW - VLDL receptor
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U2 - 10.1016/j.cca.2011.10.033
DO - 10.1016/j.cca.2011.10.033
M3 - Article
C2 - 22085424
AN - SCOPUS:84355166470
VL - 413
SP - 441
EP - 447
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
SN - 0009-8981
IS - 3-4
ER -