title: Pitavastatin inhibits remnant lipoprotein-induced macrophage foam cell formation through ApoB48 receptor-dependent mechanism.
abstract: OBJECTIVE
  Atherogenic remnant lipoproteins (RLPs) are known to induce foam cell formation in macrophages in vitro and in vivo. We examined the involvement of apoB48 receptor (apoB48R), a novel receptor for RLPs, in that process in vitro and its potential regulation by pitavastatin.
  
  
  RESULTS
  THP-1 macrophages were incubated in the presence of RLPs (20 mg cholesterol/dL, 24 hours) isolated from hypertriglyceridemic subjects. RLPs significantly increased intracellular cholesterol ester (CE) and triglyceride (TG) contents (4.8-fold and 5.8-fold, respectively) in the macrophages. Transfection of THP-1 macrophages with short interfering RNA (siRNA) against apoB48R significantly inhibited RLP-induced TG accumulation by 44%. When THP-1 macrophages were pretreated with pitavastatin (5 micromol/L, 24 hours), the expression of apoB48R was significantly decreased and RLP-induced TG accumulation was reduced by 56%. ApoB48R siRNA also inhibited TG accumulation in THP-1 macrophage induced by beta-very-low-density lipoprotein derived from apoE-/- mice by 58%, supporting the notion that apoB48R recognizes and takes-up RLPs in an apoE-independent manner.
  
  
  CONCLUSIONS
  RLPs induce macrophage foam cell formation via apoB48R. Pitavastatin inhibits RLP-induced macrophage foam cell formation. The underlying mechanism involves, at least in part, inhibition of apoB48R-dependent mechanism. Our findings indicate a potential role of apoB48R in atherosclerosis. RLPs induced macrophage foam cell formation via apoB48R. Pitavastatin inhibited RLP-induced macrophage foam cell formation, at least in part, via inhibition of apoB48R expression. Our findings indicate a potential role of apoB48R in atherosclerosis.
authors.affiliation: Department of Geriatrics and Vascular Medicine, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Kawakami
authors.forename: Mariko
authors.initials: M
authors.lastname: Tani
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Chiba
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Yui
authors.forename: Shohei
authors.initials: S
authors.lastname: Shinozaki
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Nakajima
authors.forename: Akira
authors.initials: A
authors.lastname: Tanaka
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shimokado
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D002788:Cholesterol Esters / Q000378:metabolism; D005487:Foam Cells / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D015228:Hypertriglyceridemia / Q000097:blood; D008079:Lipoproteins, VLDL / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011804:Quinolines / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D018110:Receptors, Lipoprotein / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000502:physiology
chemical_list: D001057:Apolipoproteins E; D002788:Cholesterol Esters; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008079:Lipoproteins, VLDL; D011804:Quinolines; D034741:RNA, Small Interfering; D018110:Receptors, Lipoprotein; D014280:Triglycerides; C411291:apo B48 receptor; D020742:rhoA GTP-Binding Protein; C108475:pitavastatin