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Towards non-invasive imaging of vulnerable atherosclerotic plaques by targeting co-stimulatory molecules


Müller, A; Mu, L; Meletta, R; Beck, K; Rancic, Z; Drandarov, K; Kaufmann, P A; Ametamey, S M; Schibli, R; Borel, N; Krämer, S D (2014). Towards non-invasive imaging of vulnerable atherosclerotic plaques by targeting co-stimulatory molecules. International Journal of Cardiology, 174(3):503-15.

Abstract

BACKGROUND
Myocardial infarction and stroke are the life-threatening consequences after plaque rupture in coronary or carotid arteries. Positron emission tomography employing [(18)F]fluorodeoxyglucose can visualize plaque inflammation; however, the question remains whether this is specific for plaque vulnerability. The pathophysiology of vulnerable plaques suggests several molecular processes. Here, we propose the co-stimulatory molecules CD80 and CD86 as potential new targets for non-invasive imaging.

METHODS AND RESULTS
Human atherosclerotic segments were obtained from carotid endarterectomy and classified into stable and vulnerable plaques. We identified CD80 and CD86 with significantly higher mRNA levels in vulnerable than stable plaques. CD80+ and CD86+ cells were found in spatial proximity to CD83+ dendritic cells and CD68+ macrophages of atherosclerotic plaques. As a proof of target-expression we labeled a low molecular weight ligand, which has a high affinity for human CD80, with carbon-11 to perform in vitro autoradiography with human plaque slices. We observed 3-fold higher binding to vulnerable than stable plaques, demonstrating a first approach towards discriminating between the two plaque types. Positron emission tomography studies showed accumulation in CD80+ Raji xenografts, low radioactivity in myocardium and rapid clearance from the blood pool in mice.

CONCLUSION
In human carotid arteries, the co-stimulatory molecules CD80 and CD86 show significantly higher expression levels in vulnerable compared to stable plaques. With the novel CD80-specific radiotracer we are able to discriminate between stable and vulnerable atherosclerotic plaques in vitro. This is an important step towards non-invasive imaging of the life-threatening vulnerable lesions in humans.

Abstract

BACKGROUND
Myocardial infarction and stroke are the life-threatening consequences after plaque rupture in coronary or carotid arteries. Positron emission tomography employing [(18)F]fluorodeoxyglucose can visualize plaque inflammation; however, the question remains whether this is specific for plaque vulnerability. The pathophysiology of vulnerable plaques suggests several molecular processes. Here, we propose the co-stimulatory molecules CD80 and CD86 as potential new targets for non-invasive imaging.

METHODS AND RESULTS
Human atherosclerotic segments were obtained from carotid endarterectomy and classified into stable and vulnerable plaques. We identified CD80 and CD86 with significantly higher mRNA levels in vulnerable than stable plaques. CD80+ and CD86+ cells were found in spatial proximity to CD83+ dendritic cells and CD68+ macrophages of atherosclerotic plaques. As a proof of target-expression we labeled a low molecular weight ligand, which has a high affinity for human CD80, with carbon-11 to perform in vitro autoradiography with human plaque slices. We observed 3-fold higher binding to vulnerable than stable plaques, demonstrating a first approach towards discriminating between the two plaque types. Positron emission tomography studies showed accumulation in CD80+ Raji xenografts, low radioactivity in myocardium and rapid clearance from the blood pool in mice.

CONCLUSION
In human carotid arteries, the co-stimulatory molecules CD80 and CD86 show significantly higher expression levels in vulnerable compared to stable plaques. With the novel CD80-specific radiotracer we are able to discriminate between stable and vulnerable atherosclerotic plaques in vitro. This is an important step towards non-invasive imaging of the life-threatening vulnerable lesions in humans.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nuclear Medicine
05 Vetsuisse Faculty > Institute of Veterinary Pathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:1 July 2014
Deposited On:10 Nov 2014 17:46
Last Modified:05 Apr 2016 18:00
Publisher:Elsevier
ISSN:0167-5273
Publisher DOI:https://doi.org/10.1016/j.ijcard.2014.04.071
PubMed ID:24834996

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