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In vivo fluorescence-mediated tomography imaging demonstrates atorvastatin-mediated reduction of lesion macrophages in ApoE-/- mice.

Abstract：

BACKGROUND:Macrophage recruitment into atherosclerotic plaques drives lesion progression, destabilization, and rupture. Chronic statin treatment reduces macrophage plaque content. Information on dynamics of macrophage recruitment would help assessing plaque vulnerability and guiding therapy. Techniques to image macrophage homing to vulnerable plaques in vivo are scarcely available. The authors tested if noninvasive fluorescence-mediated tomography (FMT) can assess plaque-stabilizing effects of short-term high-dosage atorvastatin. METHODS:Macrophages from green-fluorescent-protein-transgenic mice were labeled with a near-infrared fluorescent dye and were injected IV in apolipoprotein E-deficient mice (n=9) on Western diet 7 days after guidewire-injury of the carotid artery. FMT-scans, 2 and 7 days thereafter, quantified macrophage recruitment into carotid artery plaques. Atorvastatin was tested for macrophage adhesion, proliferation, and viability (n=5 to 6) in vitro. Fourteen mice received atorvastatin or vehicle for 4 days after 16 weeks on Western diet. FMT assessed macrophage recruitment into aortic and innominate artery lesions. Means (±SD)% are reported. RESULTS:Double-labeled macrophages were recruited into carotid artery lesions. FMT resolved fluorescence projecting on the injured carotid artery and detected a signal increase to 300% (±191) after guidewire injury. Atorvastatin reduced macrophage adhesion to activated endothelial cells by 36% (±19). In a clinically relevant proof-of-concept intervention, FMT-imaging detected that 4 days atorvastatin treatment reduced macrophage recruitment by 57% (±8) indicating plaque stabilization. Immunohistochemistry confirmed reduced macrophage infiltration. CONCLUSIONS:FMT optical imaging proved its high potential for clinical applicability for tracking recruitment of near-infrared fluorescent-labeled macrophages to vulnerable plaques in vivo. FMT-based quantification of macrophage recruitment demonstrated rapid plaque stabilization by 4-day atorvastatin treatment in apolipoprotein E-deficient mice.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

Larmann J,Frenzel T,Schmitz M,Hahnenkamp A,Demmer P,Immenschuh S,Tietge UJ,Bremer C,Theilmeier G

doi

10.1097/ALN.0b013e318291c18b

subject

Has Abstract

pub_date

2013-07-01 00:00:00

pages

129-41

issue

eissn

0003-3022

issn

1528-1175

journal_volume

119

pub_type

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In vivo fluorescence-mediated tomography imaging demonstrates atorvastatin-mediated reduction of lesion macrophages in ApoE-/- mice.