Circular RNA Ttc3 regulates cardiac function after myocardial infarction by sponging miR-15b

Area of Science:

• Cardiology
• Molecular Biology
• Genetics

Background:

• Apoptosis of cardiomyocytes is a key factor in cardiac remodeling post-myocardial infarction (MI).
• Circular RNAs (circRNAs) are emerging regulators of cellular functions, with circ-Ttc3 being highly expressed in the heart.
• The specific role of circ-Ttc3 in myocardial infarction has not been previously elucidated.

Purpose of the Study:

• To investigate the function and mechanism of circ-Ttc3 in myocardial infarction.
• To determine if circ-Ttc3 plays a protective role against cardiomyocyte apoptosis and cardiac dysfunction following MI.

Main Methods:

• Assessed circ-Ttc3 expression in ischemic myocardium and hypoxic cardiomyocytes.
• Utilized in vitro cell culture models with circ-Ttc3 overexpression and knockdown.
• Employed an in vivo rat model of MI with cardiac-specific circ-Ttc3 knockdown via AAV9-cTnt.
• Investigated the molecular mechanism involving miR-15b-5p and Arl2.

Main Results:

• Circ-Ttc3 expression was significantly upregulated in response to myocardial ischemia and hypoxia.
• Overexpression of circ-Ttc3 protected cardiomyocytes against hypoxia-induced ATP depletion and apoptosis, while knockdown exacerbated these effects.
• In vivo knockdown of circ-Ttc3 in a rat MI model led to worsened cardiac dysfunction.
• Circ-Ttc3 was found to sponge miR-15b-5p, consequently increasing Arl2 expression.
• Knockdown of Arl2 partially reversed the protective effects of circ-Ttc3 overexpression.

Conclusions:

• Circ-Ttc3 exhibits a significant cardioprotective role in the context of myocardial infarction.
• The protective mechanism involves the circ-Ttc3/miR-15b-5p/Arl2 regulatory axis, which mitigates cardiomyocyte apoptosis.
• Circ-Ttc3 represents a potential therapeutic target for treating heart attack-induced damage.