title: Beneficial effect of anti-platelet therapies on atherosclerotic lesion formation assessed by phase-contrast X-ray CT imaging.
abstract: We have applied an imaging system of phase-contrast X-ray CT to the detection of atherosclerotic plaque components by means of the differences of tissue mass densities. In this study, we investigated the effect of the anti-platelet therapies, widely used for secondly prevention of cardiovascular events, on plaque stability and examined whether this novel technique could detect the changes of plaque components under the therapy. Apolipoprotein E-deficient mice were fed on high-cholesterol diet alone and either with 0.1% cilostazol or clopidogrel for 10 weeks. We assessed atherosclerotic lesion volumes and components at brachiocephalic artery by the phase-contrast X-ray CT imaging and histochemistry. The phase-contrast X-ray CT imaging could reveal that cilostazol and clopidogrel significantly decreased atherosclerotic lesion volumes at brachiocephalic artery (31.2% reduction in cilostazol group and 37.4% reduction in clopidogrel group), compared with control group. In addition, the mass densities calculated by this method revealed the anti-platelet treatment increased stable plaque areas including high collagen content, but decreased unstable plaque areas including lipid and macrophage content. These findings were confirmed by histological analyses. Real-time PCR analyses indicated that anti-platelets inhibited gene expressions of cytokines and adhesion molecules, such as IFNγ and ICAM-1. Anti-platelet therapies had a beneficial effect on plaque stability maybe due to anti-inflammatory actions. Phase-contrast X-ray CT imaging could quantify the plaque volume and qualify the plaque components affected by anti-platelet therapies. This novel phase-contrast X-ray CT imaging system could be a plausible method to detect the unstable plaque non-invasively in the future.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takeda
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamashita
authors.forename: Masakazu
authors.initials: M
authors.lastname: Shinohara
authors.forename: Naoto
authors.initials: N
authors.lastname: Sasaki
authors.forename: Hideto
authors.initials: H
authors.lastname: Tawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakajima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Momose
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001835:Body Weight; D016122:Brachiocephalic Trunk / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002791:Cholesterol, Dietary; D000077407:Cilostazol; D000077144:Clopidogrel; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000494:pharmacology*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014057:Tomography, X-Ray Computed
chemical_list: D001057:Apolipoproteins E; D015815:Cell Adhesion Molecules; D002791:Cholesterol, Dietary; D016207:Cytokines; D018836:Inflammation Mediators; D008055:Lipids; D010975:Platelet Aggregation Inhibitors; D012333:RNA, Messenger; D013777:Tetrazoles; D003094:Collagen; D000077144:Clopidogrel; D000077407:Cilostazol; D013988:Ticlopidine