Key result
Macrophage-specific TFEB overexpression improves LVEF by ~10% four weeks after ischemia-reperfusion injury.
Why the study?
Inflammasome activation and IL-1β secretion are implicated in MI and resultant heart failure, but little is known about how macrophage lysosomes regulate these processes.
Does macrophage-specific TFEB overexpression attenuate postinfarction ventricular dysfunction in mice subjected to cardiac ischemia/reperfusion injury?
Population
Mice subjected to cardiac IR injury and humans with ischemic cardiomyopathy
Comparison
Macrophage-specific overexpression of TFEB vs controls
Design
Preclinical animal and human translational study
Authors
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Supports macrophage TFEB targeting in post-MI remodeling; leaves open translation from this murine model to human HF.
Does macrophage-specific TFEB overexpression attenuate postinfarction ventricular dysfunction in mice subjected to cardiac ischemia/reperfusion injury?
Absolute Event Rate: 36% vs 26%
p-value: p=<0.0001
TFEB activation in macrophages attenuates post-myocardial infarction ventricular dysfunction by reprogramming lysosomal lipid metabolism, independent of macroautophagy.
Javaheri et al. (2019) studied Myocardial infarction / Ischemia-reperfusion injury. Macrophage-specific TFEB overexpression (Mϕ-TFEB) vs. Cre-only control was evaluated on Left ventricular ejection fraction at 4 weeks (p=<0.0001). Macrophage-specific overexpression of TFEB significantly improved left ventricular ejection fraction to 36% compared to 26% in controls at 4 weeks after ischemia/reperfusion injury.
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