Photobiomodulation Therapy on Myocardial Infarction in Rats: Transcriptional and Posttranscriptional Implications to Cardiac Remodeling

Abstract

Background and Objectives: Induction of myocardial infarction (MI) in rats by occlusion of the left anterior descending coronary artery is an experimental model used in research to elucidate functional, structural, and molecular modifications associated with ischemic heart disease. Photobiomodulation therapy (PBMT) has become a therapeutic alternative by modulating various biological processes eliciting several effects, including anti-inflammatory and proproliferative actions. The main objective of this work was to evaluate the effect of PBMT in the modulation of transcriptional and post-transcriptional changes that occurred in myocardium signal transduction pathways after MI. Study Design/Materials and Methods: Continuous wave (CW) non-thermal laser parameters were: 660 nm wavelength, power 15 mW, with a total energy of 0.9 J, fluence of 1.15 J/cm 2 , spot size of 0.785 cm 2 , and time of 60 seconds. Using in silico analysis, we selected and then, quantified the expression of messenger RNA (mRNA) of 47 genes of 9 signaling pathways associated with MI (angiogenesis, cell survival, hypertrophy, oxidative stress, apoptosis, extracellular matrix, calcium kinetics, cell metabolism, and inflammation). Messenger RNA expression quantification was performed in myocardial samples by polymerase chain reaction real-time array using TaqMan customized plates. Results: Our results evidenced that MI modified mRNA expression of several well-known biomarkers related to detrimental cardiac activity in almost all signaling pathways analyzed. However, PBMT reverted most of these transcriptional changes. More expressively, PBMT provoked a robust decrease in mRNA expression of molecules that participate in post-MI inflammation and ECM composition, such as IL-6, TNF receptor, TGFb1, and collagen I and III. Global microRNA (miRNA) expression analysis revealed that PBMT decreased miR-221, miR-34c, and miR-93 expressions post-MI, which are related to deleterious effects in cardiac remodeling. Conclusion:Thus, the identification of transcriptional and post-transcriptional changes induced by PBMT may be used to interfere in the molecular dynamics of cardiac remodeling post-MI.

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

“…A progressive increase in collagens and MMPs mRNA expressions at the early phase post‐MI (first 24 hours) was detected. These observations correspond to high mRNA levels found previously by the authors at 3 days post‐MI 26 . In addition, the MI group showed significant increases in TGF‐β1, Col1a1, Col3a1, TNC, MMP‐1, and MMP‐2 mRNAs expressions in the early phase post‐MI compared to the Sham group, previous corroborating reports 28–35 .…”

“…We recently reported that PBMT modulates several signaling pathways in the myocardium after 3 days of infarction 26 . Herein, we investigated the PBMT's temporal effect in a specific pathway, the transcription regulation of cardiac fibrosis activation post‐MI.…”

“…This data corroborates the reduction in MMP-9 mRNA expression observed at the same period. 26 Osteoglycine (OGN), a contributor to cardiac fibrosis formation, is expressed at low levels by healthy myocardium. Several studies have shown that OGN mRNA expression is significantly increased after MI.…”

“…After surgery, echocardiography was performed on each period after coronary occlusion or sham surgical procedure. 26 Animals were anesthetized with intraperitoneal ketamine (100 mg/kg) and xylazine (10 mg/kg) mixture for imaging acquisition. LV measurements were performed using a 12-MHz transducer at 3 cm depth connected to an HP Sonos-5500 echocardiograph (Hewlett-Packard).…”

Light Emitting Diodes Irradiation Regulates miRNA-877-3p to Promote Cardiomyocyte Proliferation

“…MiRNAs have been reported to play a critical role in regulating key aspects of cardiac physiological and pathological signaling, including the regulation of cardiac regeneration in vitro and in vivo [40]. In a study by Feliciano et al, PBM was found to exert a regulatory effect on transcription factors associated with apoptosis within myocardial tissue of rats after myocardial infarction [41]. In addition, Allan et al found that PBM reduced the expression of miR-24 in human-induced pluripotent stem cell-derived ventricular cardiomyocytes (hiPSC-vCMs) and reduced doxorubicin induced cardiotoxicity, indicating that PBM can act at the on posttranscriptional level [42].…”