Atherosclerotic Calcification: Wnt Is the Hint

Figures

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  Figure 1. Schematic representation of inactive and activated canonical Wnt signaling. Without activation of the Frizzled receptor and the low‐density lipoprotein receptor–related protein (LRP) 5/6 coreceptor, the Axin, adenomatous polyposis coli (APC), and glycogen synthase kinase‐3 (GSK3) complex forms and phosphorylates β‐catenin, leading to its ubiquitination and subsequent degradation. Activation of canonical Wnt signaling leads to β‐catenin nuclear localization and change in expression of Wnt target genes. LEF/TCF indicates lymphoid enhancer‐binding factor/T‐cell factor.

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  Figure 2. Schematic representation of the cell polarity and Ca2+ noncanonical Wnt signaling pathways. In the cell polarity pathway, activation of particular Frizzled receptors leads to cytoskeletal rearrangement via activation of Rho and Rac GTPases. In the Ca2+ pathway, Wnt‐Frizzled receptor binding leads to increased intracellular Ca2+ concentrations from the endoplasmic reticulum. Under these conditions, nuclear factor‐κB (NF‐κB), cAMP responsive element binding, and nuclear factor associated with T cells transcription factors can translocate to the nucleus and promote an osteogenic gene profile. CamKII indicates Ca2+/calmodulin‐dependent protein kinase II; GSK3, glycogen synthase kinase‐3; IP3, inositol 1,4,5‐triphosphate; PIP2, phosphatidylinositol 4,5‐bisphosphate 2; PKC, protein kinase C; PLC, phospholipase C; and Ror2, receptor tyrosine kinaselike orphan receptor 2.

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  Figure 3. Involvement of Wnt signaling in the pathogenesis of atherosclerosis. Wnt signaling is associated with monocyte attachment, inflammation, cell proliferation, foam cell formation, and atherosclerotic calcification, ultimately leading to arterial stenosis. VSMC indicates vascular smooth muscle cell.