A review: runt-related transcription factor 2 (runx2) and its signaling pathways in cardiovascular complications.

Aliye Tabatabaee,1,* Effat farrokhi,2 Keyhan ghatre-samani,3 Narges jalilian,4

1. Student's Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran
2. Cellular and Molecular Research Center, Basic Health Science Institute, Shahrekord University of Medical Sciences
3. Cellular and Molecular Research Center, Basic Health Science Institute, Shahrekord University of Medical Sciences
4. Student's Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran

Abstract

Introduction

Vascular calcification (vc) is a process similar to bone mineralization. vc has been observed in chronic kidney disease, type 2 diabetes mellitus, and atherosclerosis, and is associated with high morbidity and mortality risk. runx2, the major transcription factor in the differentiation of osteoblasts and chondrocytes, plays a key role in differentiating vascular smooth muscle cells (vsmc) to osteoblast-like cells. this review is concerned with identifying signaling pathways which affect runx2 upregulation to have a better understanding of vc and its complications.

Methods

This review was conducted using scopus, pubmed and web of science for english articles from january 2000 to december 2016. the search keywords were “coronary artery”, “atherosclerosis”, “vascular calcification” and “runx2”.

Results

The following signaling pathways were found to be involved in runx2 upregulation: amp-activated protein kinase (ampk), protein kinase b (akt), mitogen-activated protein kinase (mapk/erk), wnt, and receptor activator of nuclear factor kappa-b (rank)and its ligand (rankl) signaling.

Conclusion

Ampk signaling pathway, specifically its ampkα subunit plays an important role in regulating runx2 sumoylation and degradation and leads to its instability through proteasome-mediated degradation in vsmcs. h2o2 – activated akt signaling is associated with increased runx2 expression and vsmc calcification. erk singling plays an important role in vsmcs calcification by regulating runx2 expression and activation. it upregulates runx2 phosphorylation and increases its activity. wnt signaling promotes osteogenesis and osteoblasts differentiation by regulating runx2 expression. bmp-wnt/ β- catenin axis has been seen in vc regulation. rank/rankl present in atherosclerosis plaques associate with vc.

Keywords

Vascular calcification, runx2, signaling pathway, atherosclerosis, coronary artery