Sclerostin and Vascular Pathophysiology.

Antonino Catalano,Nunziata Morabito,Francesco Corica,Federica Bellone

doi:10.3390/ijms21134779

Abstract

There is cumulating evidence for a contribution of Wnt signaling pathways in multiple processes involved in atherosclerosis and vascular aging. Wnt signaling plays a role in endothelial dysfunction, in the proliferation and migration of vascular smooth muscle cells (VSMCs) and intimal thickening. Moreover, it interferes with inflammation processes, monocyte adhesion and migration, as well as with foam cell formation and vascular calcification progression. Sclerostin is a negative regulator of the canonical Wnt signaling pathway and, accordingly, the consequence of increased sclerostin availability can be disruption of the Wnt signalling cascade. Sclerostin is becoming a marker for clinical and subclinical vascular diseases and several lines of evidence illustrate its role in the pathophysiology of the vascular system. Sclerostin levels increase with aging and persist higher in some diseases (e.g., diabetes, chronic kidney disease) that are known to precipitate atherosclerosis and enhance cardiovascular risk. Current knowledge on the association between sclerostin and vascular diseases is summarized in this review.

Highlights

Aging produces profound effects on the vasculature, and it is strictly associated with the development cardiovascular and cerebrovascular diseases, which are the most common causes of death among the elderly in developed countries [1]
Since several age-related cardiovascular and cerebrovascular diseases arise from alterations in arterial function, or are worsened by arterial functional and phenotypic changes, elucidating the basic mechanisms underlying arterial aging seems to be a matter of interest
A key level of its modulation occurs in the extracellular milieu due to a number of secreted Wnt antagonists including secreted frizzled related proteins and the Wnt inhibitory factor-1 (WIF1), which bond directly to Wnt molecules and alter their ability to bind to the Wnt receptor complex

Summary

Introduction

Aging produces profound effects on the vasculature, and it is strictly associated with the development cardiovascular and cerebrovascular diseases, which are the most common causes of death among the elderly in developed countries [1]. Age-induced functional and structural alterations of microcirculation play a role in the pathophysiology of a wide range of known age-related disorders, including cognitive impairment, sarcopenia and kidney or eye diseases [1,2]. The term “Wnt” is a portmanteau word derivied from the blend of the name of the Wingless segment polarity gene in drosophila and that of its vertebrate homolog, known as integrated or int-1. These conserved signalling pathways begin with proteins transmitting to the cell through its surface receptors [5]. The available evidence from in vitro and in vivo studies about Wnt proteins, receptors and antagonists, with a special focus on sclerostin, are shown below

Wnt Signaling Pathways: A Synopsis

Atherosclerosis and Wnt Signaling

Findings

Sclerostin in Atherosclerosis and Vascular Diseases