Beta‐catenin promotes macrophage‐mediated acute inflammatory response after myocardial infarction

Abstract

Regulatory mechanisms for acute inflammatory responses post myocardial infarction (MI) have yet to be fully understood. In particular, the mechanisms by which cardiac macrophages modulate MI-induced myocardial inflammation remains unclear. In this study, using a mouse MI model, we showed that β-catenin-mediated signaling was activated in cardiac macrophages post-MI, especially in Ly-6C-positive proinflammatory macrophages. Using a RAW264.7-based β-catenin reporter cell line, we confirmed the presence of active β-catenin and its downstream signaling in cardiac macrophages after MI. Moreover, lentivirus-mediated inducible expression of constitutively active β-catenin revealed that β-catenin plays a role in promoting the inflammatory response by RAW264.7 cells. Depletion of endogenous macrophages and adoptive transfer of active β-catenin-expressing RAW264.7 cells resulted in enhancement of acute myocardial inflammation in recipient mice after MI, as demonstrated by elevated levels of lymphocyte infiltrates and increased expression of proinflammatory cytokines. However, infarct volume, myocardial tissue repair, and left ventricle function were not influenced by the expression of active β-catenin in the adoptive transfer assay. Our research has demonstrated that β-catenin-mediated signaling is important for cardiac macrophages to modulate post-MI inflammatory responses. These findings may be valuable for developing novel therapeutic strategies for MI.

Signaling pathways and targeted therapy for myocardial infarction

“…Wnt-5a promotes the release of IL-1, IL-6, and IL-8 from monocytes, indicating that it has a pro-inflammatory effect 485 . β-catenin-mediated signals are activated in pro-inflammatory macrophages after MI, which is manifested by increased lymphocyte infiltration levels and increased expression of proinflammatory cytokines 486 . In addition, another study reported that the absence of Wnt inhibitory factor 1 (WIF1) causes increased inflammatory monocytes and severe adverse remodeling, while overexpression of WIF1 weakens the monocyte response and improves cardiac function 487 .…”

Signaling pathways and therapeutic interventions in gastric cancer

“… 264 – 266 The β-catenin protein is a transcriptional coactivator in Wnt pathway, which has been found to be involved in a number of biological processes of tumor cells, including proliferation, 267 , 268 anti-apoptosis, 269 and infiltration transfer. 270 The Wnt/β-catenin pathway is activated when the Wnt ligands bind to the seven-transmembrane receptor Frizzled (FZD) and the low-density lipoprotein receptor-related protein 5 or 6 (LRP5/6). 271 The Wnt-FZD-LRP5/6 trimer complex recruits disheveled (DVL) and axin through the intracellular domains of FZD and LRP5/6, thereby inhibiting β-catenin phosphorylation and ensuring β-catenin stability.…”

Critical illness and bone metabolism: where are we now and what is next?

“…Scholars found that the Wnt/β-catenin signaling was activated in cardiomyocytes located in the border region of the infarct [ 33 ]. In addition, this pathway was also activated in pro-inflammatory macrophages in the myocardial infarction area, manifested by increased levels of lymphocyte infiltration and increased expression of pro-inflammatory cytokines [ 34 ]. Another study found that loss of Wnt inhibitory factor 1 (WIF1) can lead to increased inflammatory monocytes and severe myocardial adverse remodeling, while overexpression of WIF1 impairs monocyte response and improves cardiac function [ 35 ].…”