Photobiomodulation therapy's effects on cardiac fibrosis activation after experimental myocardial infarction

Ischemic heart disease is the leading cause of death worldwide, and interventions to reduce myocardial infarction (MI) complications are widely researched. Photobiomodulation therapy (PBMT) has altered multiple biological processes in tissues and organs, including the heart.

This study aimed to assess the temporal effects of PBMT on cardiac fibrosis activation after MI in rats. In this proof-of-concept study, we monitored the change in expression patterns over time of genes and microRNAs (miRNAs) involved in the formation of cardiac fibrosis post-MI submitted to PBMT.

Experimental MI was induced, and PBMT was applied shortly after coronary artery ligation (laser light of wavelength 660 nm, 15 mW of power, energy density 22.5 J/cm² , 60 seconds of application, irradiated area 0.785 cm² , fluence 1.1 J/cm² ). Ventricular septal samples were collected at 30 minutes, 3, 6, 24 hours, and 3 days post-MI to determine temporal PBMT's effects on messenger RNA (mRNA) expression associated with cardiac fibrosis activation and miRNAs expression.

PBMT, when applied after ischemia, reversed the changes in mRNA expression of myocardial extracellular matrix genes induced by MI. Surprisingly, PBMT modified cardiac miRNAs expression related to fibrosis replacement in the myocardium. Expression correlations between myocardial mRNAs were assessed. The correlation coefficient between miRNAs and target mRNAs was also determined. A positive correlation was detected among miR-21 and transforming growth factor beta-1 mRNA. The miR-29a expression negatively correlated to Col1a1, Col3a1, and MMP-2 mRNA expressions. In addition, we observed that miR-133 and Col1a1 mRNA were negatively correlated.

The results suggest that PBMT, through the modulation of gene transcription and miRNA expressions, can interfere in cardiac fibrosis activation after MI, mainly reversing the signaling pathway of profibrotic genes.