Low-level laser therapy (LLLT) has been used as an anti-inflammatory treatment in several disease conditions, even when inflammation is a secondary consequence, such as in myocardial infarction (MI). However, the mechanism by which LLLT is able to protect the remaining myocardium remains unclear. The present study tested the hypothesis that LLLT reduces inflammation after acute MI in female rats and ameliorates cardiac function. The potential participation of the Renin-Angiotensin System (RAS) and Kallikrein-Kinin System (KKS) vasoactive peptides was also evaluated. LLLT treatment effectively reduced MI size, attenuated the systolic dysfunction after MI, and decreased the myocardial mRNA expression of interleukin-1 beta and interleukin-6 in comparison to the non-irradiated rat tissue. In addition, LLLT treatment increased protein and mRNA levels of the Mas receptor, the mRNA expression of kinin B2 receptors and the circulating levels of plasma kallikrein compared to non-treated post-MI rats. On the other hand, the kinin B1 receptor mRNA expression decreased after LLLT. No significant changes were found in the expression of vascular endothelial growth factor (VEGF) in the myocardial remote area between laser-irradiated and non-irradiated post-MI rats. Capillaries density also remained similar between these two experimental groups. The mRNA expression of the inducible nitric oxide synthase (iNOS) was increased three days after MI, however, this effect was blunted by LLLT. Moreover, endothelial NOS mRNA content increased after LLLT. Plasma nitric oxide metabolites (NOx) concentration was increased three days after MI in non-treated rats and increased even further by LLLT treatment. Our data suggest that LLLT diminishes the acute inflammation in the myocardium, reduces infarct size and attenuates left ventricle dysfunction post-MI and increases vasoactive peptides expression and nitric oxide (NO) generation.

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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.

Low-level laser therapy (LLLT) has been shown to increase the proliferation of several cell types. We evaluated the effects of LLLT on adhesion, proliferation, and gene expression of vascular endothelial growth factor (VEGF) and type 2 receptor of VEGF (VEGFR2) at mesenchymal stem cells (MSCs) from human (hMSCs) and rat (rMSCs) adipose tissues on nutritional deficiencies. A dose-response curve was performed with cells treated with laser Ga-Al-As (660 nm, 30 mW) at energy of 0.7 to 9 J. Cell adhesion and proliferation were quantified 20, 40, and 60 min after LLLT and 24, 72, and 120 h after cultivation. Gene expression was verified by RT-PCR after 2 h of LLLT. A minor nutritional support caused a significant decrease in proliferation and adhesion of hMSCs and rMSCs. However, at the lowest LLLT dose (0.7 J), we observed a higher proliferation in hMSCs at standard condition shortly after irradiation (24 h). Adhesion was higher in hMSCs cultivated in controlled conditions at higher LLLT doses (3 and 9 J), and rMSCs show a reduction in the adhesion on 1.5 to 9 J. On nutritional deprivation, a 9 J dose was shown to reduce proliferation with 24 h and adhesion to all culture times in rMSCs. VEGF and VEGFR2 were increased after LLLT in both cell types. However, hMSCs under nutritional deprivation showed higher expression of VEGF and its receptor after irradiation with other laser doses. In conclusion, LLLT on human and rat MSCs might upregulate VEGF messenger RNA (mRNA) expression and modulate cell adhesion and proliferation distinctively.

Sympathetic hyperactivity induces adverse effects in myocardial. Recent studies have shown that exercise training induces cardioprotection against sympathetic overload; however, relevant mechanisms of this issue remain unclear. We analyzed whether exercise can prevent pathological hypertrophy induced by sympathetic hyperactivity with modulation of the kallikrein-kinin and angiogenesis pathways. Male Wistar rats were assigned to non-trained group that received vehicle; non-trained isoproterenol treated group (Iso, 0.3 mg kg−1 day−1); and trained group (Iso+Exe) which was subjected to sympathetic hyperactivity with isoproterenol. The Iso rats showed hypertrophy and myocardial dysfunction with reduced force development and relaxation of muscle. The isoproterenol induced severe fibrosis, apoptosis and reduced myocardial capillary. Interestingly, exercise blunted hypertrophy, myocardial dysfunction, fibrosis, apoptosis and capillary decreases. The sympathetic hyperactivity was associated with high abundance of ANF mRNA and β-MHC mRNA, which was significantly attenuated by exercise. The tissue kallikrein was augmented in the Iso+Exe group, and kinin B1 receptor mRNA was increased in the Iso group. Moreover, exercise induced an increase of kinin B2 receptor mRNA in myocardial. The myocardial content of eNOS, VEGF, VEGF receptor 2, pAkt and Bcl-2 were increased in the Iso+Exe group. Likewise, increased expression of pro-apoptotic Bad in the Iso rats was prevented by prior exercise. Our results represent the first demonstration that exercise can modulate kallikrein-kinin and angiogenesis pathways in the myocardial on sympathetic hyperactivity. These findings suggest that kallikrein-kinin and angiogenesis may have a key role in protecting the heart.