The role of bone morphogenetic protein signaling in vascular calcification

Abstract

Vascular calcification is associated with atherosclerosis, chronic kidney disease, and diabetes, and results from processes resembling endochondral or intramembranous ossification, or from processes that are distinct from ossification. Bone morphogenetic proteins (BMP), as well as other ligands, receptors, and regulators of the transforming growth factor beta (TGFβ) family regulate vascular and valvular calcification by modulating the phenotypic plasticity of multipotent progenitor lineages associated with the vasculature or valves. While osteogenic ligands BMP2 and BMP4 appear to be both markers and drivers of vascular calcification, particularly in atherosclerosis, BMP7 may serve to protect against calcification in chronic kidney disease. BMP signaling regulators such as matrix Gla protein and BMP-binding endothelial regulator protein (BMPER) play protective roles in vascular calcification. The effects of BMP signaling molecules in vascular calcification are context-dependent, tissue-dependent, and cell-type specific. Here we review the current knowledge on mechanisms by which BMP signaling regulates vascular calcification and the potential therapeutic implications.

Keywords: Atherosclerosis; Bone morphogenetic protein; Chronic kidney disease; Diabetes; Medial calcification; Mineralization; Transforming growth factor beta; Vascular calcification; Vascular disease.

Fig. 1.

A schematic representation of the cellular sources and targets of bone morphogenetic protein (BMP) and transforming growth factor beta (TGF-beta) signaling in the vascular wall potentially contributing to vascular calcification. Arrows represent positive regulators; Diamonds represent negative regulators.