Cthrc1 Deficiency Aggravates Wound Healing and Promotes Cardiac Rupture After Myocardial Infarction via Non-Canonical WNT5A Signaling Pathway

The study investigates the role of Collagen triple helix repeat containing 1 (CTHRC1) in cardiac repair post-myocardial infarction (MI). It was found that CTHRC1 is up-regulated in cardiac fibroblasts following ischemic injury, mediated by the TGFβ1-Smad2/3 signaling axis. CTHRC1 enhances wound healing and fibroblast activation in vitro. Cthrc1 deficiency in mice led to worsened cardiac function, reduced collagen deposition, and increased mortality due to cardiac rupture post-MI. These adverse effects were associated with decreased myocardial markers and increased matrix metalloproteinases, but could be partially reversed with rCTHRC1 or rWNT5A proteins. The study concludes that CTHRC1, through the non-canonical WNT5A-PCP pathway, is crucial for wound repair and preventing cardiac rupture after MI.