Myostatin/Activin-A Signaling in the Vessel Wall and Vascular Calcification

A current hypothesis is that transforming growth factor-beta signaling ligands, such as activin-A and myostatin, play a role in vascular damage in atherosclerosis and chronic kidney disease (CKD). Myostatin and activin-A bind with different affinity the activin receptors (type I or II), activating distinct intracellular signaling pathways and finally leading to modulation of gene expression. Myostatin and activin-A are expressed by different cell types and tissues, including muscle, kidney, reproductive system, immune cells, heart, and vessels, where they exert pleiotropic effects. In arterial vessels, experimental evidence indicates that myostatin may mostly promote vascular inflammation and premature aging, while activin-A is involved in the pathogenesis of vascular calcification and CKD-related mineral bone disorders. In this review, we discuss novel insights into the biology and physiology of the role played by myostatin and activin in the vascular wall, focusing on the experimental and clinical data, which suggest the involvement of these molecules in vascular remodeling and calcification processes. Moreover, we describe the strategies that have been used to modulate the activin downward signal. Understanding the role of myostatin/activin signaling in vascular disease and bone metabolism may provide novel therapeutic opportunities to improve the treatment of conditions still associated with high morbidity and mortality.

Automated summary

The hypothesis suggests that myostatin and activin-A are involved in vascular damage in atherosclerosis and CKD, binding to different activin receptors and activating distinct signaling pathways. Myostatin promotes vascular inflammation and premature aging, while activin-A is implicated in vascular calcification and CKD-related mineral bone disorders. Understanding their roles in vascular disease and bone metabolism could lead to novel therapeutic opportunities.