title: Effects of pitavastatin on monocyte chemoattractant protein-1 in hyperlipidemic patients.
abstract: The effects of statins on platelet activation markers, chemokines and adiponectin, were investigated in 135 patients with hyperlipidemia. Of the 135 hyperlipidemic patients, 63 were allocated to the simvastatin group, treated with simvastatin at the dose of 10 mg daily, and the remaining 72 were allocated to the pitavastatin group, treated with pitavastatin at the dose of 2 mg daily. Plasma levels of platelet-derived microparticles (PDMP), cell adhesion molecules (sCD40L and sP-selectin), chemokines [monocyte chemoattractant protein-1 (MCP-1) and regulated on activation normally T-cell expressed and secreted] and adiponectin were measured at the baseline and after 6 months of treatment in both the groups. In addition, we carried out a basic study to investigate the MCP-1-dependent induction of tissue factor expression on a histiocytic cell line (U937 cells). The plasma levels of PDMP, sCD40L, sP-selectin, regulated on activation normally T-cell expressed and secreted and MCP-1 were higher, whereas those of adiponectin were lower, in the hyperlipidemic patients than in the normolipidemic controls. Plasma PDMP and sCD40L were positively correlated, whereas plasma adiponectin was negatively correlated, with the plasma levels of MCP-1. No significant differences in the plasma levels of PDMP, sCD40L, sP-selectin, regulated on activation normally T-cell expressed and secreted and MCP-1 measured before and after treatment were observed in either the simvastatin or pitavastatin group. A significant increase of the plasma adiponectin levels was observed after 6 months of treatment with pitavastatin but not after an equal duration of treatment with simvastatin. When pitavastatin-treated patients were divided into two groups according to the adiponectin response to pitavastatin treatment, significant decreases of the plasma MCP-1, PDMP and sCD40L levels were observed after pitavastatin treatment in the responder group. In the aforementioned basic study, MCP-1 by itself did not induce the expression of tissue factor on the U937 cells. However, the recombinant sCD40L-induced expression of tissue factor on U937 was enhanced by the addition of MCP-1. These findings suggest that PDMP, sCD40L and MCP-1 may participate in the development of atherothrombosis in patients with hyperlipidemia and that pitavastatin may exert an adiponectin-dependent antiatherothrombotic effect in hyperlipidemic patients.
authors.affiliation: Division of Hematology, Kishiwada City Hospital, Japan. shosaku-n@mbp.ocn.ne.jp
authors.forename: Shosaku
authors.initials: S
authors.lastname: Nomura
authors.forename: Akira
authors.initials: A
authors.lastname: Shouzu
authors.forename: Seitarou
authors.initials: S
authors.lastname: Omoto
authors.forename: Norihito
authors.initials: N
authors.lastname: Inami
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shimazu
authors.forename: Daisuke
authors.initials: D
authors.lastname: Satoh
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kajiura
authors.forename: Kohichi
authors.initials: K
authors.lastname: Yamada
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Urase
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maeda
authors.forename: Toshiji
authors.initials: T
authors.lastname: Iwasaka
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000209:etiology / Q000517:prevention & control; D023201:CD40 Ligand / Q000097:blood; D055252:Cell-Derived Microparticles; D018932:Chemokine CCL2 / Q000097:blood*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D019851:Thrombophilia / Q000209:etiology / Q000517:prevention & control; D013925:Thromboplastin / Q000096:biosynthesis; D020298:U937 Cells / Q000187:drug effects
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019007:P-Selectin; D011804:Quinolines; D023201:CD40 Ligand; D013925:Thromboplastin; C108475:pitavastatin