SMOC-1 Supports Reparative Scarring and Limits Cardiac Rupture in Myocardial Infarction Models

A study in Circulation investigated secreted modular calcium-binding protein 1 (SMOC-1) in cardiac rupture following acute myocardial infarction (AMI). Researchers compared plasma proteins in patients with and without post-AMI cardiac rupture, validated findings in additional patient cohorts and animal models, and used loss- and gain-of-function experiments to investigate causality. Outcomes included cardiac rupture, survival, and mechanisms of reparative scar formation. Sample sizes were not reported in the available abstract.

Proteomics identified 9 upregulated and 24 downregulated proteins in patients with rupture; SMOC-1 was the most significantly upregulated. A time-course study showed expression peaking 1 day after AMI and returning to baseline within a week, with cardiomyocytes identified as the predominant source. Cardiomyocyte-specific SMOC-1 deletion doubled post-AMI rupture incidence and reduced survival in mice. Adeno-associated virus serotype 9–mediated overexpression significantly reduced rupture rates, although absolute rates were not provided.

Mechanistic experiments indicated that SMOC-1 activates fibroblasts and promotes collagen synthesis and maturation. It bound TGF-β receptor 1 and recruited glutamyl-prolyl-tRNA synthetase (EPRS), activating Smad signaling; EPRS inhibition abolished its profibrotic effects. These findings suggest an endogenous repair pathway that could inform therapeutic research. However, the protective intervention evidence comes from animal models, and the abstract provides no human treatment efficacy or safety data.