S-EPMC5059718 - Leukocyte trafficking-associated vascular adhesion protein 1 is expressed and functionally active in atherosclerotic plaques. - OmicsDI

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Leukocyte trafficking-associated vascular adhesion protein 1 is expressed and functionally active in atherosclerotic plaques.

ABSTRACT: Given the important role of inflammation and the potential association of the leukocyte trafficking-associated adhesion molecule vascular adhesion protein 1 (VAP-1) with atherosclerosis, this study examined whether functional VAP-1 is expressed in atherosclerotic lesions and, if so, whether it could be targeted by positron emission tomography (PET). First, immunohistochemistry revealed that VAP-1 localized to endothelial cells of intra-plaque neovessels in human carotid endarterectomy samples from patients with recent ischemic symptoms. In low-density lipoprotein receptor-deficient mice expressing only apolipoprotein B100 (LDLR^-/-ApoB^100/100), VAP-1 was expressed on endothelial cells lining inflamed atherosclerotic lesions; normal vessel walls in aortas of C57BL/6N control mice were VAP-1-negative. Second, we discovered that the focal uptake of VAP-1 targeting sialic acid-binding immunoglobulin-like lectin 9 based PET tracer [⁶⁸Ga]DOTA-Siglec-9 in atherosclerotic plaques was associated with the density of activated macrophages (r?=?0.58, P?=?0.022). As a final point, we found that the inhibition of VAP-1 activity with small molecule LJP1586 decreased the density of macrophages in inflamed atherosclerotic plaques in mice. Our results suggest for the first time VAP-1 as a potential imaging target for inflamed atherosclerotic plaques, and corroborate VAP-1 inhibition as a therapeutic approach in the treatment of atherosclerosis.

SUBMITTER: Silvola JM

PROVIDER: S-EPMC5059718 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Leukocyte trafficking-associated vascular adhesion protein 1 is expressed and functionally active in atherosclerotic plaques.

Silvola Johanna M U JM Virtanen Helena H Siitonen Riikka R Hellberg Sanna S Liljenbäck Heidi H Metsälä Olli O Ståhle Mia M Saanijoki Tiina T Käkelä Meeri M Hakovirta Harri H Ylä-Herttuala Seppo S Saukko Pekka P Jauhiainen Matti M Veres Tibor Z TZ Jalkanen Sirpa S Knuuti Juhani J Saraste Antti A Roivainen Anne A

Scientific reports 20161012

Given the important role of inflammation and the potential association of the leukocyte trafficking-associated adhesion molecule vascular adhesion protein 1 (VAP-1) with atherosclerosis, this study examined whether functional VAP-1 is expressed in atherosclerotic lesions and, if so, whether it could be targeted by positron emission tomography (PET). First, immunohistochemistry revealed that VAP-1 localized to endothelial cells of intra-plaque neovessels in human carotid endarterectomy samples fr ...[more]

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