Wnt signaling pathway and sclerostin in the development of atherosclerosis and vascular calcification

Piotr Kocełak; Monika Puzianowska-Kuźnicka; Magdalena Olszanecka-Glinianowicz; Jerzy Chudek

doi:10.17219/acem/169567

Wnt signaling pathway and sclerostin in the development of atherosclerosis and vascular calcification

Adv Clin Exp Med. 2023 Sep 7. doi: 10.17219/acem/169567. Online ahead of print.

Authors

Piotr Kocełak¹, Monika Puzianowska-Kuźnicka^{2

3}, Magdalena Olszanecka-Glinianowicz⁴, Jerzy Chudek⁵

Affiliations

¹ Pathophysiology Unit, Department of Pathophysiology, Faculty of Medical Sciences, Medical University of Silesia, Katowice, Poland.
² Department of Geriatrics and Gerontology, Medical Centre of Postgraduate Education, Warsaw, Poland.
³ Department of Human Epigenetics, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
⁴ Health Promotion and Obesity Management Unit, Department of Pathophysiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Poland.
⁵ Department of Internal Medicine and Oncological Chemotherapy, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Poland.

PMID: 37676098
DOI: 10.17219/acem/169567

Abstract

Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and calcification. One of the pathomechanisms of atherosclerosis is the upregulation of Wnt signaling. This study aimed to summarize the current knowledge regarding the role of Wnt signaling and sclerostin in atherosclerosis, vascular calcification, aneurysms, and mortality based on the PubMed database. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendation and identified 160 papers that were included in this systematic review. The published data highlight that the upregulation of Wnt components facilitates the initiation and progression of atherosclerosis, arterial remodeling, VSMCs proliferation and phenotypic transition to the osteoblastic lineage in the arterial wall. This results in protein secretion, cell migration, calcification, fibrosis and aneurysm formation. The transformation of VSMCs into osteoblast-like cells that is observed in atherosclerosis results in sclerostin expression inhibiting the Wnt pathway. Furthermore, it was shown that sclerostin, expressed in atherosclerotic plaques, inhibits aneurysm formation in a mouse model. However, in humans, while the antisclerostin antibody romosozumab inhibits bone resorption, biochemical parameters of endothelial activation and inflammation are not affected, and the incidence of aneurysms is not increased. It was suggested that detecting sclerostin in the calcified aortic atherosclerotic plaques reflects a defense mechanism against Wnt activation and inhibition of atherosclerosis, although this has only been shown in animal models. Moreover, an increased number of vascular cells converted to osteogenic phenotypes results in increased plasma sclerostin concentrations. Therefore, plasma sclerostin derived from bone limits its importance as a global marker of vascular calcification.

Keywords: WNT-signaling; aneurysm; atherosclerosis; cardiovascular disease; sclerostin.

Publication types

Review