Characterizing the immune response to myocardial infarction in pigs

Schnitter, Florian; Stangl, Franziska; Noeske, Elisabeth; Bille, Maya; Stadtmüller, Anja; Vogt, Niklas; Sicklinger, Florian; Leuschner, Florian; Frey, Anna; Schreiber, Laura; Frantz, Stefan; Beyersdorf, Niklas; Ramos, Gustavo; Gladow, Nadine; Hofmann, Ulrich

doi:10.1007/s00395-024-01036-2

Cited by 4 publications

(1 citation statement)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Like mouse CCR2 − macrophages, the human cells are also maintained independent of monocyte recruitment and gene expression profiling revealed upregulation of genes involved in tissue morphogenesis, remodeling, and electrical conduction and downregulation of inflammatory genes. 5 Although the use of a large animal model would be beneficial for translational studies involving cardiac resident macrophages, the immune landscape of larger mammals, and nonhuman primates is poorly characterized 80 and is worthy of further investigation.…”

Section: Adaptive Tissue Remodelingmentioning

confidence: 99%

Dissecting and Visualizing the Functional Diversity of Cardiac Macrophages

Holt,

Lin,

Cicka

et al. 2024

Circulation Research

View full text Add to dashboard Cite

Cardiac macrophages represent a functionally diverse population of cells involved in cardiac homeostasis, repair, and remodeling. With recent advancements in single-cell technologies, it is possible to elucidate specific macrophage subsets based on transcriptional signatures and cell surface protein expression to gain a deep understanding of macrophage diversity in the heart. The use of fate-mapping technologies and parabiosis studies have provided insight into the ontogeny and dynamics of macrophages identifying subsets derived from embryonic and adult definitive hematopoietic progenitors that include tissue-resident and bone marrow monocyte-derived macrophages, respectively. Within the heart, these subsets have distinct tissue niches and functional roles in the setting of homeostasis and disease, with cardiac resident macrophages representing a protective cell population while bone marrow monocyte-derived cardiac macrophages have a context-dependent effect, triggering both proinflammatory tissue injury, but also promoting reparative functions. With the increased understanding of the clinical relevance of cardiac macrophage subsets, there has been an increasing need to detect and measure cardiac macrophage compositions in living animals and patients. New molecular tracers compatible with positron emission tomography/computerized tomography and positron emission tomography/ magnetic resonance imaging have enabled investigators to noninvasively and serially visualize cardiac macrophage subsets within the heart to define associations with disease and measure treatment responses. Today, advancements within this thriving field are poised to fuel an era of clinical translation.

show abstract

Section: Adaptive Tissue Remodelingmentioning

confidence: 99%

Dissecting and Visualizing the Functional Diversity of Cardiac Macrophages

Holt,

Lin,

Cicka

et al. 2024

Circulation Research

View full text Add to dashboard Cite

show abstract

Cardioprotective effects of glatiramer acetate after ischemic myocardial injury

Hofmann,

Frantz

2024

Nat Cardiovasc Res

View full text Add to dashboard Cite

Pharmacological inhibition of 11ßhydroxysteroid dehydrogenase type 1 after myocardial infarction targets extracellular matrix processing and preserves cardiac function in a translational mini-pig model

Al Disi,

Ascione,

Khan

et al. 2024

Preprint

View full text Add to dashboard Cite

Background and Purpose: Plasma glucocorticoids (GCs) increase acutely after myocardial infarction (MI), thereafter tissue levels are amplified selectively within cells expressing 11βHydroxysteroid Dehydrogenase type 1 (11βHSD1) that regenerates active GCs from circulating metabolites. GCs initially protect cardiomyocytes and prevent excessive inflammation after MI but can also suppress subsequent wound repair leading to functional decline. The present study aimed to investigate the potential of pharmacological 11βHSD1 inhibition after MI to prevent deterioration of cardiac function and its impact on wound repair. Experimental Approach: Adult female Gottingen mini-pigs underwent percutaneous balloon MI/reperfusion and were randomised to receive either oral 11βHSD1 inhibitor AZD8329 (n=11), or vehicle (n=9), from 2 until 27 days later, with concurrent administration of clinically relevant therapeutic intervention (anti-platelet, statin and ACE inhibitor). Key Results: AZD8329 treatment increased plasma accumulation of cortisone substrate consistent with successful 11βHSD1 inhibition. Gadolinium-enhanced MRI showed equivalent infarct size in both groups prior to commencing treatment. 28 days after MI cardiac function and LV area were preserved in the AZD8329 treated group relative to vehicle. There was no impact of 11βHSD1 inhibitor on neovascularisation or infarct area. Mass spectrometry imaging revealed AZD8329 binding to the healing infarct and altered regulation of extracellular matrix (ECM) processing was highlighted by birefringence microscopy and proteomic analysis. Conclusions and Implications: Pharmacological inhibition of 11βHSD1 after MI prevents deterioration of cardiac function and detrimental remodelling. 11βHSD1 inhibitors have safely reached phase 2 clinical trials in diabetes and dementia and could be repurposed as an addition to standard care after MI to prevent the development of heart failure.

show abstract

Characterizing the immune response to myocardial infarction in pigs

Cited by 4 publications

References 84 publications

Dissecting and Visualizing the Functional Diversity of Cardiac Macrophages

Dissecting and Visualizing the Functional Diversity of Cardiac Macrophages

Cardioprotective effects of glatiramer acetate after ischemic myocardial injury

Pharmacological inhibition of 11ßhydroxysteroid dehydrogenase type 1 after myocardial infarction targets extracellular matrix processing and preserves cardiac function in a translational mini-pig model

Contact Info

Product

Resources

About