Metabo-epigenetic regulatory circuits of heart disease caused by inherited and acquired lipid accumulation (A01)

遗传性和获得性脂质积累引起的心脏病的代谢表观遗传调节回路（A01）

• 批准号: 508070962
• 金额: --
• 依托单位: Institut für Experimentelle Kardiologie
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/508070962?language=en
• 关键词: Metabo; epigenetic; regulatory; circuits; heart

Inherited neutral lipid storage disease with cardiomyopathy (NLSD-CM) is caused by mutations in PNPLA2, encoding a lipid droplet (LD)-associated protein, and is characterized by massive lipid accumulation. Using mouse models of genetic and acquired NLSD-CM, we have demonstrated the involvement of histone deacetylases (HDACs) in the development of diastolic dysfunction. The aim of the project is to elucidate the molecular mechanisms by which HDACs regulate lipid metabolism and cardiac function, to unravel the metabo-epigenetic circuits connecting chromatin state with metabolic and lysosomal-autophagic control in NLSD-CM.

遗传性中性脂质沉积病伴心肌病（NLSD-CM）是由编码脂滴（LD）相关蛋白的PNPLA 2突变引起的，其特征是大量脂质蓄积。使用遗传性和获得性NLSD-CM的小鼠模型，我们已经证明了组蛋白脱乙酰酶（HDAC）参与舒张功能障碍的发展。该项目的目的是阐明HDAC调节脂质代谢和心脏功能的分子机制，以解开NLSD-CM中连接染色质状态与代谢和溶酶体自噬控制的代谢-表观遗传回路。