Department of Pharmacology and Toxicology, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.
Department of Pharmacology and Toxicology, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA,
Cell Physiol Biochem. 2021 May 22;55(3):277-300. doi: 10.33594/000000373.
The lysosome is a single ubiquitous membrane-enclosed intracellular organelle with an acidic pH present in all eukaryotic cells, which contains large numbers of hydrolytic enzymes with their maximal enzymatic activity at a low pH (pH ≤ 5) such as proteases, nucleases, and phosphatases that are able to degrade extracellular and intracellular components. It is well known that lysosomes act as a center for degradation and recycling of large numbers of macromolecules delivered by endocytosis, phagocytosis, and autophagy. Lysosomes are recognized as key organelles for cellular clearance and are involved in many cellular processes and maintain cellular homeostasis. Recently, it has been shown that lysosome function and its related pathways are of particular importance in vascular regulation and related diseases. In this review, we highlighted studies that have improved our understanding of the connection between lysosome function and vascular physiological and pathophysiological activities in arterial smooth muscle cells (SMCs) and endothelial cells (ECs). Sphingolipids-metabolizingenzymes in lysosomes play critical roles in intracellular signaling events that influence cellular behavior and function in SMCs and ECs. The focus of this review will be to define the mechanism by which the lysosome contributes to cardiovascular regulation and diseases. It is believed that exploring the role of lysosomal function and its sphingolipid metabolism in the initiation and progression of vascular disease and regulation may provide novel insights into the understanding of vascular pathobiology and helps develop more effective therapeutic strategies for vascular diseases.
溶酶体是一种普遍存在的单层膜包裹的细胞内细胞器，存在于所有真核细胞中，其内部含有大量的水解酶，这些酶在低 pH 值（pH ≤ 5）时具有最大的酶活性，如蛋白酶、核酸酶和磷酸酶，能够降解细胞外和细胞内的成分。众所周知，溶酶体作为内吞作用、吞噬作用和自噬作用所递送的大量大分子物质的降解和再循环的中心发挥作用。溶酶体被认为是细胞清除的关键细胞器，参与许多细胞过程并维持细胞内稳态。最近，已经表明溶酶体的功能及其相关途径在血管调节和相关疾病中具有特别重要的作用。在这篇综述中，我们强调了一些研究，这些研究提高了我们对溶酶体功能与动脉平滑肌细胞（SMCs）和内皮细胞（ECs）中血管生理和病理生理活性之间联系的理解。溶酶体中的鞘脂代谢酶在影响 SMCs 和 ECs 中细胞行为和功能的细胞内信号事件中发挥着关键作用。这篇综述的重点将是定义溶酶体对心血管调节和疾病的贡献机制。人们相信，探索溶酶体功能及其鞘脂代谢在血管疾病的发生和发展中的作用以及调节作用可能为理解血管病理生物学提供新的见解，并有助于为血管疾病开发更有效的治疗策略。
