Dataset Information

Detection of cardiac apoptosis by [¹⁸F]ML-10 in a mouse model of permanent LAD ligation.

ABSTRACT:

Purpose

The loss of viable cardiac cells and cell death by myocardial infarction (MI) is still a significant obstacle in preventing deteriorating heart failure. Imaging of apoptosis, a defined cascade to cell death, could identify areas at risk.

Procedures

Using 2-(5-[¹⁸F]fluoropentyl)-2-methyl-malonic acid ([¹⁸F]ML-10) in autoradiography and positron emission tomography (PET) visualized apoptosis in murine hearts after permanent ligation of the left anterior descending artery (LAD) inducing myocardial infarction (MI). 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) PET imaging localized the infarct area after MI. Histology by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining validated apoptosis in the heart.

Results

Accumulation of [¹⁸F]ML-10 was evident in the infarct area after permanent ligation of the LAD in autoradiography and PET imaging. Detection of apoptosis by [¹⁸F]ML-10 is in line with the defect visualized by [¹⁸F]FDG and the histological approach.

Conclusion

[¹⁸F]ML-10 could be a suitable tracer for apoptosis imaging in a mouse model of permanent LAD ligation.

SUBMITTER: Fischer M

PROVIDER: S-EPMC9296384 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Detection of cardiac apoptosis by [<sup>18</sup>F]ML-10 in a mouse model of permanent LAD ligation.

Fischer Maximilian M Olivier Jessica J Lindner Simon S Zacherl Mathias J MJ Massberg Steffen S Bartenstein Peter P Ziegler Sibylle S Brendel Matthias M Lehner Sebastian S Boening Guido G Todica Andrei A

Molecular imaging and biology 20220329 4

<h4>Purpose</h4>The loss of viable cardiac cells and cell death by myocardial infarction (MI) is still a significant obstacle in preventing deteriorating heart failure. Imaging of apoptosis, a defined cascade to cell death, could identify areas at risk.<h4>Procedures</h4>Using 2-(5-[<sup>18</sup>F]fluoropentyl)-2-methyl-malonic acid ([<sup>18</sup>F]ML-10) in autoradiography and positron emission tomography (PET) visualized apoptosis in murine hearts after permanent ligation of the left anterior ...[more]

PMID: 35352214

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Project description:Objectives: Decellularized extracellular matrix (dECM) is increasingly used in a wide range of regenerative medicine applications and may also offer the potential to support injured myocardium. Here, we evaluated the myocardial gene expression pattern after myocardial infarction (MI) in a standardized rodent LAD-ligation model with and without ventricular stabilization with a customized, cardiac dECM-based scaffold (cdECM). Methods: MI was induced in male Wistar rats by standard LAD-ligation and confirmed 14 days post-intervention by echocardiographic parameters (FAS<40%). Cardiac ECM from donor rats was used to generate individual cdECM-scaffolds (tissue engineered myocardial sleeve, TEMS), which were epicardially implanted after confirmed MI for ventricular stabilization. After 4 and 8 weeks heart function was assessed by echocardiography, rats were sacrificed and explanted hearts were analyzed. In addition to histological analysis, standardized anterior left ventricular wall myocardial tissue samples were assessed by quantitative real-time PCR evaluating the specific gene expression pattern for immunomodulatory (IL-10, TGFBR2, TNFα), pro-angiogenic (VEGFA, FGF2, PGF, PDGFB), pro-survival (HGF, SDF1, IGF1, AKT1), remodeling-associated (TIMP1, MMP2, MMP9) and infarction-specific (NPPA, NPPB) markers. Results: Ventricular stabilization led to integration of the TEMS-scaffold into the myocardial scar with varying degrees of cellular infiltration, as well as significantly improved echocardiographic parameters demonstrating attenuation of maladaptive cardiac remodeling. Further, TEMS implantation after MI altered the myocardial gene expression pattern. Differences in gene expression were most striking after 4 weeks with significantly reduced expression of NPPA (0.36 ± 0.26 vs 0.75 ± 0.40; p < 0.05), NPPB (0.47 ± 0.25 vs 0.91 ± 0.429; p < 0.01), TGFBR2 (0.68 ± 0.16 vs 0.90 ± 0.14; p < 0.01) and PDGFB (0.81 ± 0.13 vs 1.06 ± 0.14; p < 0.01) as well as increased expression of IL-10 (5.93 ± 5.67 vs 1.38 ± 0.60; p < 0.05), PGF (1.48 ± 0.38 vs 1.09 ± 0.25; p < 0.05) and IGF1 (1.67 ± 0.70 vs 1.03 ± 0.42; p < 0.05). However, after 8 weeks differences in the gene expression patterns of remodeling-associated, and pro-angiogenic markers could still be observed between groups. Conclusion: Ventricular stabilization via TEMS implantation after MI did not only led to biological integration of the cdECM-scaffolds into the host tissue and improved functional cardiac parameters, but also altered 4 and 8 week gene expression of infarcted myocardium, possibly contributing to reducing chronic deteriorating effects while increasing the potential for myocardial regeneration.

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Dataset Information

Detection of cardiac apoptosis by [¹⁸F]ML-10 in a mouse model of permanent LAD ligation.

Purpose

Procedures

Results

Conclusion

Publications

Detection of cardiac apoptosis by [<sup>18</sup>F]ML-10 in a mouse model of permanent LAD ligation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Detection of cardiac apoptosis by [18F]ML-10 in a mouse model of permanent LAD ligation.

Purpose

Procedures

Results

Conclusion

Publications

Detection of cardiac apoptosis by [<sup>18</sup>F]ML-10 in a mouse model of permanent LAD ligation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Detection of cardiac apoptosis by [¹⁸F]ML-10 in a mouse model of permanent LAD ligation.