Intimal smooth muscle cells up-regulate beta-very low density lipoprotein-mediated cholesterol accumulation by enhancing beta-very low density lipoprotein uptake and decreasing cholesterol efflux.
To clarify the mechanism of smooth muscle cell (SMC)-derived foam cell formation, we investigated beta-very low density lipoprotein (beta-VLDL) cholesterol metabolism in vascular medial SMCs (M-SMCs) from normal rabbits compared with intimal SMCs (I-SMCs) from normal rabbits fed a high-cholesterol diet and LDL receptor-deficient rabbits. For both types of I-SMCs, uptake of [3H]cholesteryl oleate labeled beta-VLDL increased 1.6 times and release of [3H]cholesterol decreased 40% compared with M-SMCs. M-SMCs took up part of the beta-VLDL through the LDL receptor but I-SMCs did not. mRNAs for the VLDL receptor and the LDL receptor relative with 11 ligand binding repeats were expressed at similar levels in all SMCs. M-SMCs expressed more LDL receptor-related protein than I-SMCs. Ligand blotting analysis revealed greater 125I-beta-VLDL binding to a 700-kDa protein in I-SMCs compared with M-SMCs. I-SMCs had higher activities of acid cholesterol esterase and acyl-CoA:cholesterol acyltransferase, and lower activity of neutral cholesterol esterase than M-SMCs in both the absence and the presence of beta-VLDL. These results indicate that I-SMCs accumulate more cholesteryl ester than M-SMCs by taking up more beta-VLDL and by effluxing less cholesterol.
Ishii
Itsuko
I
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33, Yayoi-cho, Inage-ku, 263-8522, Chiba, Japan. iishii@p.chiba-u.ac.jp
Satoh
Hidemi
H
Kawachi
Hirokazu
H
Jingami
Hisato
H
Matsuoka
Naoki
N
Ohmori
Shigeru
S
Bujo
Hideaki
H
Yamamoto
Tokuo
T
Saito
Yasushi
Y
Kitada
Mitsukazu
M
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D011817:Rabbits; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D014316:Tritium; D017539:Tunica Intima / Q000378:metabolism; D017540:Tunica Media / Q000378:metabolism; D015854:Up-Regulation
D007457:Iodine Radioisotopes; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; C036053:VLDL receptor; D014316:Tritium; D002784:Cholesterol