Lysosomal dysfunction in vascular smooth muscle cells: Mechanisms and therapeutic targets in vascular disease

Vascular smooth muscle cell (VSMC) dysfunction is a common feature of atherosclerosis, aortic aneurysms, vascular calcification, and other vascular diseases. In VSMCs, lysosomes play an essential role in autophagic degradation, endocytic cargo processing, intracellular recycling, and cellular stress responses. Under pathological conditions, lysosomal dysfunction promotes foam cell formation, osteogenic differentiation, and extracellular matrix remodeling in VSMCs, thereby contributing to vascular diseases. This review summarizes current evidence on the role of lysosomal dysfunction in VSMC biology, its contribution to vascular diseases, and the molecular mechanisms involved. We also discuss strategies to restore lysosomal function and the challenges of targeting lysosomal pathways in VSMCs. A better understanding of VSMC-specific lysosomal regulation may facilitate the development of therapeutic strategies for vascular diseases.