PET imaging of myocardial healing following myocardial infarction (MI) could have prognostic value and aid novel therapeutic development. Stimulation of peripheral α7 nicotinic acetylcholine receptors (α7nAChR) is known to promote many aspects of myocardial healing, including inhibition of inflammation and promotion of angiogenesis. We hypothesised that α7nAChR could serve as a marker of myocardial healing with early expression due to angiogenic activity. Therefore, we set out to assess the temporal expression of α7nAChR in rat MI tissue using the α7nAChR-specific radiotracer NS14490, in addition to histology and proteomic profiling.
Adult male Sprague-Dawley rats underwent coronary artery ligation (30 mins) followed by reperfusion to induce MI (n=4-5), or sham-surgery (n=4-6), before culling and collecting their hearts at d2, d7, d14 and d28. α7nAChR was detected by autoradiography using [3H]NS14490 in wax processed tissue, with serial sections used for histology. d2 and d28 fresh frozen infarct tissue was used for proteomics.
Proteomics and histology (CD68+ve macrophage and collagen) demonstrate early dominance of inflammation followed by later extracellular matrix (ECM) deposition. α7nAChR imaging revealed that expression starts at d14 and peaks at d28 post-injury, almost exclusively within the infarct territory. α7nAChR expression strongly correlated with total collagen levels.
This expression pattern does not support a role for α7nAChR in early angiogenesis in this model, but is consistent with a role in regulation of ECM deposition after resolution of inflammation. Further investigation is required to ascertain how the level of α7nAChR measured by NS14490 relates to myocardial repair and long term functional outcome.
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