Colasante Claudia, Chen Jiangping, Ahlemeyer Barbara, Baumgart-Vogt Eveline
Eveline Baumgart-Vogt, Institute for Anatomy and Cell Biology II, Division of Medical Cell Biology, University of Giessen, 35392 Giessen, Germany, E-mail:
Thromb Haemost. 2015 Mar;113(3):452-63. doi: 10.1160/TH14-06-0497. Epub 2015 Jan 22.
It is well established that the heart is strongly dependent on fatty acid metabolism. In cardiomyocytes there are two distinct sites for the β-oxidisation of fatty acids: the mitochondrion and the peroxisome. Although the metabolism of these two organelles is believed to be tightly coupled, the nature of this relationship has not been fully investigated. Recent research has established the significant contribution of mitochondrial function to cardiac ATP production under normal and pathological conditions. In contrast, limited information is available on peroxisomal function in the heart. This is despite these organelles harbouring metabolic pathways that are potentially cardio-protective, and findings that patients with peroxisomal diseases, such as adult Refsum´s disease, can develop heart failure. In this article, we provide a comprehensive overview on the current knowledge of peroxisomes and the regulation of lipid metabolism by PPARs in cardiomyocytes. We also present new experimental evidence on the differential expression of peroxisome-related genes in the heart chambers and demonstrate that even a mild peroxisomal biogenesis defect (Pex11α-/-) can induce profound alterations in the cardiomyocyte´s peroxisomal compartment and related gene expression, including the concomitant deregulation of specific PPARs. The possible impact of peroxisomal dysfunction in the heart is discussed and a model for the modulation of myocardial metabolism via a peroxisome/PPAR-loop is proposed.
众所周知，心脏强烈依赖脂肪酸代谢。在心肌细胞中，脂肪酸的β氧化有两个不同的位点：线粒体和过氧化物酶体。尽管人们认为这两种细胞器的代谢紧密相关，但这种关系的本质尚未得到充分研究。最近的研究证实了线粒体功能在正常和病理条件下对心脏ATP生成的重要贡献。相比之下，关于心脏中过氧化物酶体功能的信息有限。尽管这些细胞器具有潜在的心脏保护代谢途径，而且诸如成人Refsum病等过氧化物酶体疾病患者会出现心力衰竭，但情况依然如此。在本文中，我们全面概述了目前关于过氧化物酶体以及心肌细胞中PPARs对脂质代谢调节的认识。我们还展示了关于心脏腔室中过氧化物酶体相关基因差异表达的新实验证据，并证明即使是轻度的过氧化物酶体生物发生缺陷（Pex11α-/-）也会导致心肌细胞过氧化物酶体区室和相关基因表达的深刻改变，包括特定PPARs的伴随失调。本文讨论了过氧化物酶体功能障碍在心脏中的可能影响，并提出了一个通过过氧化物酶体/PPAR环调节心肌代谢的模型。
