Blocking Wnt5a signaling decreases CD36 expression and foam cell formation in atherosclerosis

Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology
Ian AckersRamiro Malgor

Abstract

Wnt5a is a highly studied member of the Wnt family and recently has been implicated in the pathogenesis of atherosclerosis, but its precise role is unknown. Foam cell development is a critical process to atherosclerotic plaque formation. In the present study, we investigated the role of noncanonical Wnt5a signaling in the development of foam cells. Human carotid atherosclerotic tissue and THP-1-derived macrophages were used to investigate the contribution of Wnt5a signaling in the formation of foam cells. Immunohistochemistry was used to evaluate protein expression of scavenger receptors and noncanonical Wnt5a receptors [frizzled 5 (Fz5) and receptor tyrosine kinase-like orphan receptor 2 (Ror2)] in human atherosclerotic macrophages/foam cells. Changes in protein expression in response to Wnt5a stimulation/inhibition were determined by Western blot, and lipid accumulation was evaluated by fluorescent lipid droplet staining. Wnt5a (P<.05), Fz5 (P<.01), and Ror2 (P<.01) were significantly expressed in advanced atherosclerotic lesions compared to less advanced lesions (N=10). Wnt5a, Fz5, and Ror2 were expressed in macrophages/foam cells within the plaque. In vitro studies revealed that Wnt5a significantly increased the expression ...Continue Reading

Citations

Sep 20, 2019·Science Translational Medicine·Ioannis AkoumianakisCharalambos Antoniades
Aug 11, 2020·Current Atherosclerosis Reports·Kunming TianSuowen Xu
Jun 27, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Kamyar Asadipooya, Ada Weinstock
Nov 20, 2020·Cardiovascular Research·Hongyang ShuDao Wen Wang
Jan 29, 2021·Journal of Cellular Physiology·Jun LiHuimin Bian

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