ADAMTS4-specific MR probe to assess aortic aneurysms in vivo using synthetic peptide libraries

Jan O Kaufmann; Julia Brangsch; Avan Kader; Jessica Saatz; Dilyana B Mangarova; Martin Zacharias; Wolfgang E Kempf; Timm Schwaar; Marco Ponader; Lisa C Adams; Jana Möckel; Rene M Botnar; Matthias Taupitz; Lars Mägdefessel; Heike Traub; Bernd Hamm; Michael G Weller; Marcus R Makowski

doi:10.1038/s41467-022-30464-8

ADAMTS4-specific MR probe to assess aortic aneurysms in vivo using synthetic peptide libraries

Jan O Kaufmann, Julia Brangsch, Avan Kader, Jessica Saatz, Dilyana B Mangarova, Martin Zacharias, Wolfgang E Kempf, Timm Schwaar, Marco Ponader, Lisa C Adams, Jana Möckel, Rene M Botnar, Matthias Taupitz, Lars Mägdefessel, Heike Traub, Bernd Hamm, Michael G Weller, Marcus R Makowski

Biomedical Engineering Department

Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Federal Institute for Materials Research and Testing (BAM)
Center of Functional Protein Assemblies
Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar,Technical University Munich, Munich, Germany.; Department of Medicine, Karolinska Institutet, Stockholm, Sweden.; DZHK, partner Site Munich Heart Alliance, Munich, Germany.
School of Biomedical Engineering and Imaging Sciences
Charité University of Medicine Berlin
Radiology Department

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

136 Downloads (Pure)

Abstract

The incidence of abdominal aortic aneurysms (AAAs) has substantially increased during the last 20 years and their rupture remains the third most common cause of sudden death in the cardiovascular field after myocardial infarction and stroke. The only established clinical parameter to assess AAAs is based on the aneurysm size. Novel biomarkers are needed to improve the assessment of the risk of rupture. ADAMTS4 (A Disintegrin And Metalloproteinase with ThromboSpondin motifs 4) is a strongly upregulated proteoglycan cleaving enzyme in the unstable course of AAAs. In the screening of a one-bead-one-compound library against ADAMTS4, a low-molecular-weight cyclic peptide is discovered with favorable properties for in vivo molecular magnetic resonance imaging applications. After identification and characterization, it's potential is evaluated in an AAA mouse model. The ADAMTS4-specific probe enables the in vivo imaging-based prediction of aneurysm expansion and rupture.

Original language	English
Article number	2867
Pages (from-to)	2867
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-30464-8
Publication status	Published - 23 May 2022

Keywords

Animals
Aortic Aneurysm, Abdominal/diagnostic imaging
Disease Models, Animal
Disease Progression
Magnetic Resonance Imaging
Mice
Peptide Library
Risk Factors

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ADAMTS4-specific MR probe_KAUFMANN_Publishedonline23May2022_GOLD VoR CC BYFinal published version, 9.07 MBLicence: CC BY

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Kaufmann, J. O., Brangsch, J., Kader, A., Saatz, J., Mangarova, D. B., Zacharias, M., Kempf, W. E., Schwaar, T., Ponader, M., Adams, L. C., Möckel, J., Botnar, R. M., Taupitz, M., Mägdefessel, L., Traub, H., Hamm, B., Weller, M. G., & Makowski, M. R. (2022). ADAMTS4-specific MR probe to assess aortic aneurysms in vivo using synthetic peptide libraries. Nature Communications, 13(1), 2867. Article 2867. https://doi.org/10.1038/s41467-022-30464-8

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title = "ADAMTS4-specific MR probe to assess aortic aneurysms in vivo using synthetic peptide libraries",

abstract = "The incidence of abdominal aortic aneurysms (AAAs) has substantially increased during the last 20 years and their rupture remains the third most common cause of sudden death in the cardiovascular field after myocardial infarction and stroke. The only established clinical parameter to assess AAAs is based on the aneurysm size. Novel biomarkers are needed to improve the assessment of the risk of rupture. ADAMTS4 (A Disintegrin And Metalloproteinase with ThromboSpondin motifs 4) is a strongly upregulated proteoglycan cleaving enzyme in the unstable course of AAAs. In the screening of a one-bead-one-compound library against ADAMTS4, a low-molecular-weight cyclic peptide is discovered with favorable properties for in vivo molecular magnetic resonance imaging applications. After identification and characterization, it's potential is evaluated in an AAA mouse model. The ADAMTS4-specific probe enables the in vivo imaging-based prediction of aneurysm expansion and rupture.",

keywords = "Animals, Aortic Aneurysm, Abdominal/diagnostic imaging, Disease Models, Animal, Disease Progression, Magnetic Resonance Imaging, Mice, Peptide Library, Risk Factors",

author = "Kaufmann, {Jan O} and Julia Brangsch and Avan Kader and Jessica Saatz and Mangarova, {Dilyana B} and Martin Zacharias and Kempf, {Wolfgang E} and Timm Schwaar and Marco Ponader and Adams, {Lisa C} and Jana M{\"o}ckel and Botnar, {Rene M} and Matthias Taupitz and Lars M{\"a}gdefessel and Heike Traub and Bernd Hamm and Weller, {Michael G} and Makowski, {Marcus R}",

note = "Funding Information: This study was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project-ID 372486779—SFB 1340 2018; MA 5943/3-1/4-1/9-1 and the BHF program grant—RG/12/1/29262. J.O.K. thanks Dr. Teresia Hallstr{\"o}m from NanoTemper and Dr. Zolt{\'a}n Konthur from BAM 1.8 for assistance with MST measurements. L.C.A. is grateful for her participation in the BIH Charit{\'e}-Clinician Scientist Program funded by the Charit{\'e}-Universitaetsmedizin Berlin and the Berlin Institute of Health. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = may,

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doi = "10.1038/s41467-022-30464-8",

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Kaufmann, JO, Brangsch, J, Kader, A, Saatz, J, Mangarova, DB, Zacharias, M, Kempf, WE, Schwaar, T, Ponader, M, Adams, LC, Möckel, J, Botnar, RM, Taupitz, M, Mägdefessel, L, Traub, H, Hamm, B, Weller, MG & Makowski, MR 2022, 'ADAMTS4-specific MR probe to assess aortic aneurysms in vivo using synthetic peptide libraries', Nature Communications, vol. 13, no. 1, 2867, pp. 2867. https://doi.org/10.1038/s41467-022-30464-8

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T1 - ADAMTS4-specific MR probe to assess aortic aneurysms in vivo using synthetic peptide libraries

AU - Kaufmann, Jan O

AU - Brangsch, Julia

AU - Kader, Avan

AU - Saatz, Jessica

AU - Mangarova, Dilyana B

AU - Zacharias, Martin

AU - Kempf, Wolfgang E

AU - Schwaar, Timm

AU - Ponader, Marco

AU - Adams, Lisa C

AU - Möckel, Jana

AU - Botnar, Rene M

AU - Taupitz, Matthias

AU - Mägdefessel, Lars

AU - Traub, Heike

AU - Hamm, Bernd

AU - Weller, Michael G

AU - Makowski, Marcus R

N1 - Funding Information: This study was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project-ID 372486779—SFB 1340 2018; MA 5943/3-1/4-1/9-1 and the BHF program grant—RG/12/1/29262. J.O.K. thanks Dr. Teresia Hallström from NanoTemper and Dr. Zoltán Konthur from BAM 1.8 for assistance with MST measurements. L.C.A. is grateful for her participation in the BIH Charité-Clinician Scientist Program funded by the Charité-Universitaetsmedizin Berlin and the Berlin Institute of Health. Publisher Copyright: © 2022, The Author(s).

PY - 2022/5/23

Y1 - 2022/5/23

N2 - The incidence of abdominal aortic aneurysms (AAAs) has substantially increased during the last 20 years and their rupture remains the third most common cause of sudden death in the cardiovascular field after myocardial infarction and stroke. The only established clinical parameter to assess AAAs is based on the aneurysm size. Novel biomarkers are needed to improve the assessment of the risk of rupture. ADAMTS4 (A Disintegrin And Metalloproteinase with ThromboSpondin motifs 4) is a strongly upregulated proteoglycan cleaving enzyme in the unstable course of AAAs. In the screening of a one-bead-one-compound library against ADAMTS4, a low-molecular-weight cyclic peptide is discovered with favorable properties for in vivo molecular magnetic resonance imaging applications. After identification and characterization, it's potential is evaluated in an AAA mouse model. The ADAMTS4-specific probe enables the in vivo imaging-based prediction of aneurysm expansion and rupture.

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KW - Animals

KW - Aortic Aneurysm, Abdominal/diagnostic imaging

KW - Disease Models, Animal

KW - Disease Progression

KW - Magnetic Resonance Imaging

KW - Mice

KW - Peptide Library

KW - Risk Factors

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U2 - 10.1038/s41467-022-30464-8

DO - 10.1038/s41467-022-30464-8

M3 - Article

C2 - 35606349

SN - 2041-1723

VL - 13

SP - 2867

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2867

ER -

ADAMTS4-specific MR probe to assess aortic aneurysms in vivo using synthetic peptide libraries

Abstract

Keywords

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