Key result
Nasal administration of troponin subunits prior to or 1 hour after myocardial ischemia-reperfusion injury in mice decreased infarct size by 40% at 24 hours and 50% at 1.5 months.
Why the study?
Does nasal administration of troponin reduce infarct size and improve cardiac function in mice with myocardial ischemia-reperfusion injury?
Does nasal administration of troponin reduce infarct size and improve cardiac function in mice with myocardial ischemia-reperfusion injury?
Effect estimate: 40% reduction at 24 h; 50% reduction at 1.5 months
Nasal vaccination with troponin induces IL-10-secreting CD4+ T cells that reduce infarct size and improve cardiac function following myocardial ischemia-reperfusion injury in a mouse model.
May inform mucosal tolerance strategies post-MI/R; leaves open human translation and clinical trials.
Myocardial ischemia with subsequent reperfusion (MI/R) can lead to significant myocardial damage. Ischemia initiates inflammation at the blood-microvascular endothelial cell interface and contributes significantly to both acute injury and repair of the damaged tissue. We have found that MI/R injury in mice is associated with a cellular immune response to troponin. Myocardial cells exclusively synthesize troponin and release the troponin into the bloodstream following injury. Mucosally administered proteins induce T cells that secrete anti-inflammatory cytokines such as IL-10 and transforming growth factor beta at the anatomical site where the protein localizes. We found that nasal administration of the three subunits of troponin (C, I and T isoforms), given prior to or 1 h following MI/R, decreased infarct size by 40% measured 24 h later. At 1.5 months following MI/R, there was a 50% reduction in infarct size and improvement in cardiac function as measured by echocardiography. Protection was associated with a reduction of cellular immunity to troponin. Immunohistochemistry demonstrated increased IL-10 and reduced IFN-gamma in the area surrounding the ischemic infarct following nasal troponin. Adoptive transfer of CD4+ T cells to mice from nasally troponin-treated mice 1 h after the MI/R decreased infarct size by 72%, whereas CD4+ T cells from IL-10-/- mice or nasally BSA-treated mice had no effect. Our results demonstrate that IL-10-secreting CD4+ T cells induced by nasal troponin reduce injury following MI/R. Modulation of cardiac inflammation by nasal troponin provides a novel treatment to decrease myocardial damage and enhance recovery after myocardial ischemia.
No takes yet. Share an insight, caveat, or question.
Frenkel et al. (2009) studied Myocardial ischemia-reperfusion injury. Nasal administration of troponin (C, I and T isoforms) vs. Control (BSA-treated mice) was evaluated on Infarct size (40% reduction at 24 h; 50% reduction at 1.5 months). Nasal administration of troponin subunits prior to or 1 hour after myocardial ischemia-reperfusion injury in mice decreased infarct size by 40% at 24 hours and 50% at 1.5 months.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: