LncRNA PEG10 aggravates cardiac hypertrophy through regulating HOXA9

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Non-coding RNA Research

Background:

• Cardiac hypertrophy is a significant risk factor for heart failure.
• Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cardiovascular diseases.
• The specific role of lncRNA PEG10 in cardiac hypertrophy remains unclear.

Purpose of the Study:

• To investigate the role of lncRNA PEG10 in the progression of cardiac hypertrophy.
• To elucidate the regulatory mechanism of PEG10 on HOXA9 in cardiac hypertrophy.

Main Methods:

• Establishment of in vivo (transverse aortic constriction model) and in vitro (phenylephrine treatment) cardiac hypertrophy models.
• Quantification of PEG10, ANP, and BNP levels in cardiac tissues and primary cardiomyocytes.
• Assessment of HOXA9's regulatory effects on cardiomyocyte surface area and biomarker expression.
• Exploration of the PEG10/HOXA9 regulatory loop's impact on cardiomyocyte hypertrophy.

Main Results:

• PEG10, ANP, and BNP levels were significantly elevated in the transverse aortic constriction (TAC) group compared to the sham group.
• Phenylephrine treatment upregulated PEG10, ANP, and BNP in primary cardiomyocytes, while si-PEG10 transfection downregulated them.
• PEG10 inhibition reduced the PE-induced increase in cardiomyocyte surface area.
• HOXA9 knockdown mimicked the effects of PEG10 inhibition, and si-HOXA9 reversed PEG10-induced hypertrophy.

Conclusions:

• PEG10 is upregulated in hypertrophic cardiomyocytes.
• PEG10 exacerbates cardiac hypertrophy by positively regulating HOXA9.
• The PEG10/HOXA9 axis represents a potential therapeutic target for cardiac hypertrophy.