| Autor: |
Lewis, Andrew J.M., Miller, Jack J., Lau, Angus Z., Curtis, Mary K., Rider, Oliver J., Choudhury, Robin P., Neubauer, Stefan, Cunningham, Charles H., Carr, Carolyn A., Tyler, Damian J. |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
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| Zdroj: |
Lewis, A J M, Miller, J J, Lau, A Z, Curtis, M K, Rider, O J, Choudhury, R P, Neubauer, S, Cunningham, C H, Carr, C A & Tyler, D J 2018, ' Noninvasive immunometabolic cardiac inflammation imaging using hyperpolarized magnetic resonance ', Circulation research, vol. 122, no. 8, pp. 1084-1093 . https://doi.org/10.1161/CIRCRESAHA.117.312535 |
| DOI: |
10.1161/CIRCRESAHA.117.312535 |
| Popis: |
Rationale: Current cardiovascular clinical imaging techniques offer only limited assessment of innate immune cell-driven inflammation, which is a potential therapeutic target in myocardial infarction (MI) and other diseases. Hyperpolarized magnetic resonance (MR) is an emerging imaging technology that generates contrast agents with 10- to 20 000-fold improvements in MR signal, enabling cardiac metabolite mapping. Objective: To determine whether hyperpolarized MR using [1-13C]pyruvate can assess the local cardiac inflammatory response after MI. Methods and Results: We performed hyperpolarized [1-13C]pyruvate MR studies in small and large animal models of MI and in macrophage-like cell lines and measured the resulting [1-13C]lactate signals. MI caused intense [1-13C]lactate signal in healing myocardial segments at both day 3 and 7 after rodent MI, which was normalized at both time points after monocyte/macrophage depletion. A near-identical [1-13C]lactate signature was also seen at day 7 after experimental MI in pigs. Hyperpolarized [1-13C]pyruvate MR spectroscopy in macrophage-like cell suspensions demonstrated that macrophage activation and polarization with lipopolysaccharide almost doubled hyperpolarized lactate label flux rates in vitro; blockade of glycolysis with 2-deoxyglucose in activated cells normalized lactate label flux rates and markedly inhibited the production of key proinflammatory cytokines. Systemic administration of 2-deoxyglucose after rodent MI normalized the hyperpolarized [1-13C]lactate signal in healing myocardial segments at day 3 and also caused dose-dependent improvement in IL (interleukin)-1β expression in infarct tissue without impairing the production of key reparative cytokines. Cine MRI demonstrated improvements in systolic function in 2-DG (2-deoxyglucose)-treated rats at 3 months. Conclusions: Hyperpolarized MR using [1-13C]pyruvate provides a novel method for the assessment of innate immune cell-driven inflammation in the heart after MI, with broad potential applicability across other cardiovascular disease states and suitability for early clinical translation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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