Key result
Systemic IL-1α deficiency reduces myocardial inflammation and protects against adverse LV remodeling and dysfunction post-MI.
Why the study?
While IL-1β and IL-1 receptor inhibition dampen post-MI inflammation, the potential role of IL-1α in post-MI inflammation and adverse ventricular remodeling has received much less attention.
Does systemic or cardiomyocyte-specific IL-1α deletion reduce myocardial inflammation and attenuate ventricular remodeling in a murine model of myocardial infarction?
Does systemic or cardiomyocyte-specific IL-1α deletion reduce myocardial inflammation and attenuate ventricular remodeling in a murine model of myocardial infarction?
Systemic deletion of IL-1α, but not cardiomyocyte-specific deletion, protects against adverse cardiac remodeling and inflammation following myocardial infarction in mice, suggesting systemic anti-IL-1α therapies may be beneficial.
May support systemic IL-1α inhibition post-MI; hypothesis-generating in animal models only.
Myocardial inflammation following myocardial infarction (MI) is crucial for proper myocardial healing, yet, dysregulated inflammation may promote adverse ventricular remodeling and heart failure. IL-1 signaling contributes to these processes, as shown by dampened inflammation by inhibition of IL-1β or the IL-1 receptor. In contrast, the potential role of IL-1α in these mechanisms has received much less attention. Previously described as a myocardial-derived alarmin, IL-1α may also act as a systemically released inflammatory cytokine. We therefore investigated the effect of IL-1α deficiency on post-MI inflammation and ventricular remodeling in a murine model of permanent coronary occlusion. In the first week post-MI, global IL-1α deficiency (IL-1α KO mice) led to decreased myocardial expression of IL-6, MCP-1, VCAM-1, hypertrophic and pro-fibrotic genes, and reduced infiltration with inflammatory monocytes. These early changes were associated with an attenuation of delayed left ventricle (LV) remodeling and systolic dysfunction after extensive MI. In contrast to systemic Il1a-KO, conditional cardiomyocyte deletion of Il1a (CmIl1a-KO) did not reduce delayed LV remodeling and systolic dysfunction. In conclusion, systemic Il1a-KO, but not Cml1a-KO, protects against adverse cardiac remodeling after MI due to permanent coronary occlusion. Hence, anti-IL-1α therapies could be useful to attenuate the detrimental consequences of post-MI myocardial inflammation.
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Lugrin et al. (2023) studied Myocardial infarction. Systemic IL-1α deficiency (IL-1α KO) vs. Conditional cardiomyocyte deletion of Il1a (CmIl1a-KO) and wild-type controls was evaluated on Post-MI inflammation and ventricular remodeling. Systemic IL-1α deficiency, but not conditional cardiomyocyte deletion, decreased myocardial inflammation and protected against adverse left ventricular remodeling and systolic dysfunction post-MI.
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