Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People's Republic of China.
Cardiovascular Surgery Laboratory, Renmin Hospital of Wuhan University, 9# Zhangzhidong Road, Wuhan 430000, Hubei Province, People's Republic of China.
Food Funct. 2022 Jul 18;13(14):7666-7683. doi: 10.1039/d2fo01084d.
Iron deficiency (ID) is a global nutritional deficiency that was shown to be involved in the pathogenesis of aortic aneurysm and dissection (AAD) in our previous studies. Some studies suggested that mitochondrial dynamics was involved in the apoptosis and phenotypic transformation of vascular smooth muscle cells (VSMCs). However, little is known about the role of mitochondrial dynamics in aortic medial degeneration (AMD) promoted by an iron deficient diet. The present study investigated the effect of ID on the phenotypic transformation of VSMCs, the progression of AMD, and the underlying mechanism. The expression of p-Drp1 (Ser616) and Fis1 was markedly upregulated in the aortic media of AAD patients and ApoE mice with subcutaneous AngII osmotic pumps. ID facilitated the formation of mitochondria-associated endoplasmic reticulum membranes (MAMs), which triggered excessive mitochondrial fission, induced the phenotypic transformation of VSMCs, and ultimately accelerated the progression of AMD. Furthermore, the present study indicated that an inhibitor of Drp1 could partially reverse this process. Maintaining iron balance in the human body may prevent the development of AAD.
缺铁（ID）是一种全球性的营养缺乏症，我们之前的研究表明它与主动脉瘤和夹层（AAD）的发病机制有关。一些研究表明，线粒体动力学参与了血管平滑肌细胞（VSMCs）的凋亡和表型转化。然而，对于缺铁饮食促进的主动脉中层退行性变（AMD）中线粒体动力学的作用知之甚少。本研究探讨了 ID 对 VSMCs 表型转化、AMD 进展的影响及其潜在机制。在 AAD 患者和皮下 AngII 渗透泵的 ApoE 小鼠的主动脉中层中，p-Drp1（Ser616）和 Fis1 的表达明显上调。缺铁促进了线粒体相关内质网膜（MAMs）的形成，这引发了过度的线粒体分裂，诱导了 VSMCs 的表型转化，最终加速了 AMD 的进展。此外，本研究表明，Drp1 的抑制剂可以部分逆转这一过程。维持人体铁平衡可能有助于预防 AAD 的发生。
