Vascular Smooth Muscle Cell Neutral Sphingomyelinase 2 in the Release of Exosomes and Vascular Calcification

Vascular calcification (VC) is the pathological precipitation of calcium salts in the walls of blood vessels. It is a risk factor for cardiovascular events and their associated mortality. VC can be observed in a variety of cardiovascular diseases and is most prominent in diseases that are associated with dysregulated mineral homeostasis such as in chronic kidney disease. Local factors and mechanisms underlying VC are still incompletely understood, but it is appreciated that VC is a multifactorial process in which vascular smooth muscle cells (VSMCs) play an important role. VSMCs participate in VC by releasing extracellular vesicles (EVs), the extent, composition, and propensity to calcify of which depend on VSMC phenotype and microenvironment. Currently, no targeted therapy is available to treat VC. In-depth knowledge of molecular players of EV release and the understanding of their mechanisms constitute a vital foundation for the design of pharmacological treatments to combat VC effectively. This review highlights our current knowledge of VSMCs in VC and focuses on the biogenesis of exosomes and the role of the neutral Sphingomyelinase 2 (nSMase2).

Automated summary

Vascular calcification is the pathological deposition of calcium salts in blood vessel walls and is a risk factor for cardiovascular events and mortality. Vascular smooth muscle cells (VSMCs) play a crucial role in this process by releasing extracellular vesicles (EVs), but the underlying mechanisms are not fully understood. Understanding the molecular factors and mechanisms of EV release is essential for developing targeted pharmacological treatments for vascular calcification.