PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Kimm, M.A.* ; Haas, H.* ; Stölting, M.* ; Kuhlmann, M.* ; Geyer, C.* ; Glasl, S. ; Schäfers, M.* ; Ntziachristos, V. ; Wildgruber, M.* ; Höltke, C.*

Targeting endothelin receptors in a murine model of myocardial infarction using a small molecular fluorescent probe.

Mol. Pharm. 17, 109-117 (2020)
Postprint Forschungsdaten DOI PMC
Open Access Green
The endothelin (ET) axis plays a pivotal role in cardiovascular diseases. Enhanced levels of circulating ET-1 have been correlated with an inferior clinical outcome after myocardial infarction (MI) in humans. Thus, the evaluation of endothelin-A receptor (ETAR) expression over time in the course of myocardial injury and healing may offer valuable information toward the understanding of the ET axis involvement in MI. We developed an approach to track the expression of ETAR with a customized molecular imaging probe in a murine model of MI. The small molecular probe based on the ETAR-selective antagonist 3-(1,3-benzodioxol-5-yl)-5-hydroxy-5-(4-methoxyphenyl)-4-[(3,4,5-trimethoxyphenyOmethyl]-2(5H)-furanone (PD156707) was labeled with fluorescent dye, IRDye800cw. Mice undergoing permanent ligation of the left anterior descending artery (LAD) were investigated at day 1, 7, and 21 post surgery after receiving an intravenous injection of the ETAR probe. Cryosections of explanted hearts were analyzed by cryotome-based CCD, and fluorescence reflectance imaging (FRI) and fluorescence signal intensities (SI) were extracted. Fluorescence-mediated tomography (FMT) imaging was performed to visualize probe distribution in the target region in vivo. An enhanced fluorescence signal intensity in the infarct area was detected in cryoCCD images as early as day 1 after surgery and intensified up to 21 days post MI. FRI was capable of detecting significantly enhanced SI in infarcted regions of hearts 7 days after surgery. In vivo imaging by FMT localized enhanced SI in the apex region of infarcted mouse hearts. We verified the localization of the probe and ETAR within the infarct area by immunohistochemistry (IHC). In addition, neovascularized areas were found in the affected myocardium by CD31 staining. Our study demonstrates that the applied fluorescent probe is capable of delineating ETAR expression over time in affected murine myocardium after MI in vivo and ex vivo.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
4.321
1.132
2
2
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Endothelin Axis ; Myocardial Infarction ; Molecular Imaging ; Optical Imaging; Left-ventricular Dysfunction; Acute Heart-failure; Prognostic Information; Plasma-concentrations; Big Endothelin-1; Up-regulation; No-reflow; Expression; System; Rat
Sprache englisch
Veröffentlichungsjahr 2020
Prepublished im Jahr 2019
HGF-Berichtsjahr 2019
ISSN (print) / ISBN 1543-8384
e-ISSN 1543-8392
Zeitschrift Molecular Pharmaceutics
Quellenangaben Band: 17, Heft: 1, Seiten: 109-117 Artikelnummer: , Supplement: ,
Verlag American Chemical Society (ACS)
Verlagsort 1155 16th St, Nw, Washington, Dc 20036 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Biological and Medical Imaging (IBMI)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-505500-001
DOI 10.1021/acs.molpharmaceut.9b00810
WOS ID WOS:000506713600011
Scopus ID 85077085635
PubMed ID 31816245
Erfassungsdatum 2020-01-13
[➜Korrektur melden]