Peroxisomes as modulatory units in heart metabolism and heart failure (A10)

在A10中，我们发现过氧体对心脏功能是必不可少的。我们发现，在小鼠和人类的心力衰竭(HF)中，过氧化物酶体都会发生变化。我们建立了一种新的小鼠模型，该模型具有心脏特异性的过氧化物体功能敲除，并观察到心脏中功能过氧化酶体的缺乏会导致严重的扩张型心肌病(DCM)和心力衰竭。细胞HF表型与脂类代谢、脂类储存和线粒体形态的剧烈变化有关。我们的目标是破译将过氧化物酶代谢功能与心脏功能和心衰联系起来的分子机制。

In A10, we discovered that peroxisomes are essential for cardiac function. We found that peroxisomes are altered in heart failure (HF) in mice and in humans. We established a novel mouse model with cardiac-specific knockout of peroxisome function and observed that lack of functional peroxisomes in the heart leads to severe dilated cardiomyopathy (DCM) and heart failure. The cellular HF phenotype is associated with drastic alterations in lipid metabolism, lipid storage, and mitochondrial morphology. We aim to decipher the molecular mechanisms that link peroxisome metabolic function to heart function and HF.