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Contrast enhanced ultrasound molecular imaging of vascular inflammation in atherosclerosis: development of methods for early detection of cardiovascular risk and assessment of the effect of targeted therapies

English title Contrast enhanced ultrasound molecular imaging of vascular inflammation in atherosclerosis: development of methods for early detection of cardiovascular risk and assessment of the effect of targeted therapies
Applicant Kaufmann Beat
Number 141603
Funding scheme Ambizione
Research institution Klinik für Kardiologie Bereich Medizin Universitätsspital Basel
Institution of higher education University of Basel - BS
Main discipline Cardiovascular Research
Start/End 01.04.2012 - 31.03.2014
Approved amount 367'424.00
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Keywords (12)

Atherosclerosis; Molecular imaging; Echocardiography; Inflammation; Therapy; Contrast; Echocardiography; Contrast; Atherosclerosis; Molecular imaging; Therapy; Inflammation

Lay Summary (English)

Lead
Lay summary
Atherosclerosis leads to heart attacks, stroke and other diseases, and in the western world is the single most frequent cause for morbidity and mortality. Current treatment strategies focus on palliating the late complications of atherosclerosis (e.g. treatment of a "heart attack"). However, atherosclerosis is an immunoinflammatory disease that commences decades before it leads to clinical consequences. Important players in the pathogenesis of atherosclerosis are receptors on the inner lining of blood vessel, the so called endothelium. These receptors are responsible for the uptake of cholesterol into the vessel wall, which causes inflammation and the expression of yet another family of receptors that are responsible for the recruitment of white blood cells into the vessel wall. Recruitment of white blood cells leads to an amplification of the inflammatory reaction and, together with the deposition of cholesterol and the immigration of other cells into the vessel wall, over the years results in the buildup of atheroscerotic plaques. It is generally thought, that in vivo imaging of the expression of the above mentioned receptors can be used for early detection and risk stratification fof atherosclerosis. Contrast enhanced ultrasound molecular imaging uses small microbubbles that can be detected with ultrasound after they have been injected into a living organism. These microbubbles can be specifically targeted to receptors that are present on the endothelium by conjugation of antibodies or peptides onto the microbubble surface. In the present research proposal, we propose (1) to develop a antibody-targeted microbubble to an endothelial receptor that is responsible for the uptake of cholesterol into the vessel wall, which is expressed throughout the pathogenesis of atherosclerosis, and (2) to develop a microbubble that is targeted to an endothelial receptor for white blood cells using a small peptide ligands. The latter research aim is based on the notion that for clinical applications, small peptide ligands may offer advantages in terms of target specificity, cost and availability.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Molecular imaging of inflammation and platelet adhesion in advanced atherosclerosis effects of antioxidant therapy with NADPH oxidase inhibition.
Liu Yani, Kaufmann Beat, Lindner Jonathan (2013), Molecular imaging of inflammation and platelet adhesion in advanced atherosclerosis effects of antioxidant therapy with NADPH oxidase inhibition., in Circulation Cardiovascular Imaging, 6(1), 74-82.
Molecular Imaging Reveals Rapid Reduction of Endothelial Activation in Early Atherosclerosis With Apocynin Independent of Antioxidative Properties.
Khanicheh Elham, Qi Yue, Xie Aris, Mitterhuber Martina, Xu Lifen, Mochizuki Michika, Daali Youssef, Jaquet Vincent, Krause Karlheinz, Ruggeri Zaverio, Kuster Gabriela, Lindner Jonathan, Kaufmann Beat (2013), Molecular Imaging Reveals Rapid Reduction of Endothelial Activation in Early Atherosclerosis With Apocynin Independent of Antioxidative Properties., in ATVB, 33(9), 2187-2192.
Noninvasive ultrasound molecular imaging of the effect of statins on endothelial inflammatory phenotype in early atherosclerosis.
Khanicheh Elham, Mitterhuber Martina, Xu Lifen, Haeuselmann Stephanie, Kuster Gabriela, Kaufmann Beat (2013), Noninvasive ultrasound molecular imaging of the effect of statins on endothelial inflammatory phenotype in early atherosclerosis., in PLOS One, 8(3), e58761-e58761.
Detection of antecedent myocardial ischemia with multiselectin molecular imaging.
Davidson Brian, Kaufmann Beat, Lindner Jonathan (2012), Detection of antecedent myocardial ischemia with multiselectin molecular imaging., in Journal of the American College of Cardiology, 60(17), 1690-1697.
Factors affecting the endothelial retention of targeted microbubbles: influence of microbubble shell design and cell surface projection of the endothelial target molecule.
Khanicheh Elham, Kaufmann Beat (2012), Factors affecting the endothelial retention of targeted microbubbles: influence of microbubble shell design and cell surface projection of the endothelial target molecule., in JASE, 25(4), 460-466.

Collaboration

Group / person Country
Types of collaboration
OHSU United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Awards

Title Year
Young Investigator Award Finalist Euroecho 2012 Vienna, Austria 2012

Associated projects

Number Title Start Funding scheme
149718 Non-invasive ultrasound molecular imaging of myocarditis and autoimmune myocardial inflammation 01.04.2014 Project funding (Div. I-III)
123819 Contrast enhanced ultrasound molecular imaging of vascular inflammation in atherosclerosis: development of methods for early detection of cardiovascular risk and assessment of the effect of targeted therapies 01.04.2009 Ambizione

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