Secreted frizzled-related protein 1 (Sfrp1) alleviates myocardial injury and delays heart failure progression through a multi-pathway interaction network including Wnt, Hippo, and Notch pathways.
Sfrp1 is a multi-target intervention molecule that offers a novel mechanistic approach to treating heart failure by interrupting the cycle of injury and decompensation.
Heart failure (HF) is a clinical syndrome characterized by impairment of the heart's pumping function. Its core pathological basis is the vicious cycle of "injury reconstruction decompensation" triggered by cardiomyocyte damage. This review aims to systematically elucidate the molecular mechanism by which secreted frizzled-related protein 1 (Sfrp1; all proteins mentioned in the article are mouse genes, and Sfrp1 is used as the abbreviation) alleviates myocardial injury and delays the progression of HF through a multi-pathway interaction network. The main contents include (1) the core pathological mechanism of HF, such as oxidative stress (excessive ROS leads to calcium overload and mitochondrial apoptosis), autophagy disorder (the AngII/β5i axis inhibits protective autophagy), and abnormal apoptosis (imbalance of Bax/Bcl-2 triggers cardiomyocyte loss); (2) the structural features of Sfrp1, a secretory glycoprotein rich in cysteine domains (CRD), which inhibits the classical Wnt/β-catenin pathway by competitively binding to Wnt ligands; (3) the Sfrp1 six-layer protective mechanisms of Sfrp1: antagonizing the Wnt pathway to reduce ROS production and fibrosis; activating the Hippo/Notch pathways to inhibit pathological proliferation; promoting autophagy; downregulating Bax/Cyt c/Caspase-3; upregulating Bcl-2 to inhibit apoptosis; and improving calcium metabolism disorders by upregulating SERCA2a/MICU1. The conclusion suggests that coordinated regulation of these pathways by Sfrp1 interrupts the vicious cycle of HF. As a multi-target intervention molecule, Sfrp1 offers a novel approach to the targeted treatment of HF.
He et al. (Fri,) conducted a review in Heart failure. Secreted frizzled-related protein 1 (Sfrp1) was evaluated. Secreted frizzled-related protein 1 (Sfrp1) alleviates myocardial injury and delays heart failure progression through a multi-pathway interaction network including Wnt, Hippo, and Notch pathways.