Coronary disease & ACSResearch article
Identification of Secreted Modular Calcium-Binding Protein 1 as a Novel Endogenous Protective Molecule Against Acute Myocardial Infarction–Induced Cardiac Rupture
- unbiased proteomics analysis
- loss- and gain-of-function animal models
Authors' conclusion
Our study provides the first evidence that the transient upregulation and secretion of cardiomyocyte-derived SMOC-1 constitute an intrinsic profibrotic and antirupture response to severe ischemic injury. However, this natural protective mechanism is insufficient to fully prevent cardiac rupture, highlighting the potential of enhancing the SMOC-1 pathway as a promising therapeutic strategy to mitigate cardiac rupture and reduce AMI-associated mortality.
Study context
- Population
- Patients with acute myocardial infarction (AMI) and animal models (AMI mice)
- Comparison
- patients with AMI with cardiac rupture compared with those without
Main finding
As reported in the abstract
proteins significantly upregulated
9
proteins significantly downregulated
24
Further findings
SMOC-1 expression time course
- Transiently elevated, peaking 1 day after AMI and returning to baseline within a week
- Cardiomyocytes the predominant source of SMOC-1
Post-AMI cardiac rupture and survival
- Cardiomyocyte-specific SMOC-1 knockout doubled the incidence of post-AMI cardiac rupture and reduced survival
- Adeno-associated virus serotype 9-mediated SMOC-1 overexpression significantly decreased cardiac rupture rates
Mechanism
- Cardiomyocyte-derived SMOC-1 supports fibrosis by activating fibroblasts, enhancing collagen synthesis, and promoting collagen maturation
- SMOC-1 binds TGF-βR1 in fibroblasts, recruiting EPRS to form a signaling complex that activates the Smad pathway
- Inhibiting EPRS abolished the profibrotic effects of SMOC-1
Original publication
Summarised from the published abstract; every number is checked against it