Multiparametric Immunoimaging Maps Inflammatory Signatures in Murine Myocardial Infarction Models

Alexander Maier, Yohana C. Toner, Jazz Munitz, Nathaniel A.T. Sullivan, Ken Sakurai, Anu E. Meerwaldt, Eliane E.S. Brechbühl, Geoffrey Prévot, Yuri van Elsas, Rianne J.F. Maas, Anna Ranzenigo, Georgios Soultanidis, Mohammad Rashidian, Carlos Pérez-Medina, Gyu Seong Heo, Robert J. Gropler, Yongjian Liu, Thomas Reiner, Matthias Nahrendorf, Filip K. SwirskiGustav J. Strijkers, Abraham J.P. Teunissen, Claudia Calcagno, Zahi A. Fayad, Willem J.M. Mulder, Mandy M.T. van Leent

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

In the past 2 decades, research on atherosclerotic cardiovascular disease has uncovered inflammation to be a key driver of the pathophysiological process. A pressing need therefore exists to quantitatively and longitudinally probe inflammation, in preclinical models and in cardiovascular disease patients, ideally using non-invasive methods and at multiple levels. Here, we developed and employed in vivo multiparametric imaging approaches to investigate the immune response following myocardial infarction. The myocardial infarction models encompassed either transient or permanent left anterior descending coronary artery occlusion in C57BL/6 and Apoe−/−mice. We performed nanotracer-based fluorine magnetic resonance imaging and positron emission tomography (PET) imaging using a CD11b-specific nanobody and a C-C motif chemokine receptor 2-binding probe. We found that immune cell influx in the infarct was more pronounced in the permanent occlusion model. Further, using 18F-fluorothymidine and 18F-fluorodeoxyglucose PET, we detected increased hematopoietic activity after myocardial infarction, with no difference between the models. Finally, we observed persistent systemic inflammation and exacerbated atherosclerosis in Apoe−/− mice, regardless of which infarction model was used. Taken together, we showed the strengths and capabilities of multiparametric imaging in detecting inflammatory activity in cardiovascular disease, which augments the development of clinical readouts.

Original languageEnglish
Pages (from-to)801-816
Number of pages16
JournalJACC: Basic to Translational Science
Volume8
Issue number7
DOIs
StatePublished - Jul 2023

Keywords

  • MI
  • atherosclerosis
  • imaging
  • immunology
  • inflammation

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