Cardiac Myocyte-Specific Overexpression of FASTKD1 Prevents Ventricular Rupture After Myocardial Infarction

Area of Science:

• Cardiology
• Molecular Biology
• Biochemistry

Background:

• Mitochondrial mRNA-binding protein FASTKD1 (Fas-activated serine/threonine kinase domain-containing protein 1) shows in vitro protective effects against oxidative stress in myocytes.
• The in vivo role of FASTKD1 in the myocardium remains undetermined.

Purpose of the Study:

• To investigate the effects of cardiac-specific FASTKD1 overexpression on experimental myocardial infarction (MI) in vivo.
• To assess FASTKD1's impact on cardiac function, rupture resistance, and cellular responses post-MI.

Main Methods:

• Generated cardiac-specific FASTKD1 transgenic mice with varying expression levels.
• Subjected mice to permanent coronary ligation to induce myocardial infarction.
• Analyzed cardiac morphology, function, mitochondrial parameters, inflammatory cell infiltration, extracellular matrix components, antioxidant capacity, apoptosis, and gene expression.

Main Results:

• FASTKD1 overexpression did not affect baseline cardiac morphology, function, or mitochondrial parameters.
• Transgenic mice showed 0% left ventricular free wall rupture post-MI compared to 40% in controls.
• FASTKD1 overexpression led to reduced neutrophil infiltration, increased macrophage infiltration, elevated periostin, and enhanced antioxidant capacity, associated with integrated stress response activation.

Conclusions:

• Cardiac-specific FASTKD1 overexpression confers resistance to MI-induced cardiac rupture in mice.
• FASTKD1 modulates inflammatory, extracellular matrix, and antioxidant responses post-MI.
• Enhanced activation of the integrated stress response is linked to FASTKD1's protective effects in myocardial infarction.