Department of Cardiology, The Second Affiliated Hospital of Guilin Medical University, Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin, 541100, Guangxi, China.
Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin, Guangxi, China.
Cell Commun Signal. 2022 May 7;20(1):60. doi: 10.1186/s12964-022-00858-8.
Apolipoprotein A-I binding protein (AIBP), a secreted protein, has been shown to play a pivotal role in the development of atherosclerosis. The function of intracellular AIBP, however, is not yet well characterized. Here, we found that AIBP is abundantly expressed within human and mouse atherosclerotic lesions and exhibits a distinct localization in the inner membrane of mitochondria in macrophages. Bone marrow-specific AIBP deficiency promotes the progression of atherosclerosis and increases macrophage infiltration and inflammation in low-density lipoprotein receptor-deficient (LDLR) mice. Specifically, the lack of mitochondrial AIBP leads to mitochondrial metabolic disorders, thereby reducing the formation of mitophagy by promoting the cleavage of PTEN-induced putative kinase 1 (PINK1). With the reduction in mitochondrial autophagy, macrophages polarize to the M1 proinflammatory phenotype, which further promotes the development of atherosclerosis. Based on these results, mitochondrial AIBP in macrophages performs an antiatherosclerotic role by regulating of PINK1-dependent mitophagy and M1/M2 polarization. Video Abstract.
载脂蛋白 A-I 结合蛋白 (AIBP) 是一种分泌蛋白，它在动脉粥样硬化的发展中起着关键作用。然而，细胞内 AIBP 的功能尚未得到很好的描述。在这里，我们发现 AIBP 在人和鼠的动脉粥样硬化病变中大量表达，并在巨噬细胞的线粒体内膜上表现出独特的定位。骨髓特异性 AIBP 缺乏会促进动脉粥样硬化的进展，并增加低密度脂蛋白受体缺陷 (LDLR) 小鼠中巨噬细胞的浸润和炎症。具体来说，线粒体 AIBP 的缺乏会导致线粒体代谢紊乱，从而通过促进 PTEN 诱导的假定激酶 1 (PINK1) 的裂解来促进自噬的形成。随着线粒体自噬的减少，巨噬细胞向 M1 促炎表型极化，这进一步促进了动脉粥样硬化的发展。基于这些结果，巨噬细胞中的线粒体 AIBP 通过调节 PINK1 依赖性自噬和 M1/M2 极化来发挥抗动脉粥样硬化作用。视频摘要。
