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.

The impact of prenatal alcohol exposure (PAE) varies considerably between individuals, leading to morphological and genetic changes. However, minor changes usually go undetected in PAE children. We investigated PAE’s effects on gene transcription of genes related to cardiac dysfunction signaling in mouse myocardium and morphological changes. C57Bl/6 mice were subjected to a 10% PAE protocol. In postnatal days 2 and 60 (PN2 and PN60), morphometric measurements in the offspring were performed. Ventricular samples of the heart were collected in PN60 from male offspring for quantification of mRNA expression of 47 genes of nine myocardial signal transduction pathways related to cardiovascular dysfunction. Animals from the PAE group presented low birth weight than the Control group, but the differences were abolished in adult mice. In contrast, the mice’s size was similar in PN2; however, PAE mice were oversized at PN60 compared with the Control group. Cardiac and ventricular indexes were increased in PAE mice. PAE modulated the mRNA expression of 43 genes, especially increasing the expressions of genes essential for maladaptive tissue remodeling. PAE animals presented increased antioxidant enzyme activities in the myocardium. In summary, PAE animals presented morphometric changes, transcription of cardiac dysfunction-related genes, and increased antioxidant protection in the myocardium.

Introduction: 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.Objectives: 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. Materials and Methods: 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/cm 2 , 60 seconds of application, irradiated area 0.785 cm 2 , fluence 1.1 J/cm 2 ). 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. Results: 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. Conclusion: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.

Prenatal alcohol exposure (PAE) impairs fetal development. Alcohol consumption was shown to modulate the renin–angiotensin system (RAS). This study aimed to analyze the effects of PAE on the expression of the renin–angiotensin system (RAS) and kallikrein–kinin system (KKS) peptide systems in the hippocampus and heart of mice of both sexes. C57Bl/6 mice were exposed to alcohol during pregnancy at a concentration of 10% (v/v). On postnatal day 45 (PN45), mouse hippocampi and left ventricles (LV) were collected and processed for messenger RNA (mRNA) expression of components of the RAS and KKS. In PAE animals, more pronounced expression of AT1 and ACE mRNAs in males and a restored AT2 mRNA expression in females were observed in both tissues. In LV, increased AT2, ACE2, and B2 mRNA expressions were also observed in PAE females. Furthermore, high levels of H2O2 were observed in males from the PAE group in both tissues. Taken together, our results suggest that modulation of the expression of these peptidergic systems in PAE females may make them less susceptible to the effects of alcohol.

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Epilepsy is a prevalent and serious brain condition, characterized by the recurrence of unprovoked seizures. Disturbances on cellular processes, which are controlled by post‐transcriptional gene expression modulations such as microRNAs (miRNAs) can lower multiple proteins expressions within molecular pathways. In order to elucidate the role miRNAs exert in the hippocampus from rats with epilepsy induced by pilocarpine, expression of miRNAs was quantified by NanoString technology. Furthermore, miRNA targets were identified by in silico analysis. We observed strong changes in miRNA expression profiles in hippocampal cells derived from epileptic rats compared to the control. MiRNAs to be related to inflammation and oxidative stress were found differentially expressed in silico analysis. For instance, in hippocampal tissue, miR‐146 emerged, which are known to interact with interleukin‐6, a major player in inflammatory process. Expression change was observed for let‐7, which targets IL‐6 as well. Further differentially expressed miRNAs were related to oxidative stress and generation of reactive oxygen species, such as miR‐30e. Altogether, the data indicate that miRNAs are an interesting starting point for functional and mechanistic epilepsy research. Support or Funding Information 1) Universidade Nove de Julho, UNINOVE, São Paulo, Brazil 2) Universidade São Camilo, São Paulo, Brazil 3) Nova Southeastern University, NSU, Florida, USA

Introdução: Os efeitos do consumo de álcool durante o período gestacional ainda não são bem compreendidos, mas é sabido que pode levar a alterações celulares importantes modificando o desenvolvimento fetal. Estima-se que 20% das gestantes consumam álcool durante toda a gestação, mesmo que em pequenas doses. O impacto potencial da Exposição Pré-natal ao Álcool (EPA) varia consideravelmente entre os indivíduos, podendo levar a alterações morfológicas como defeitos congênitos no coração. Entretanto, muitas dessas alterações ocorrem silenciosamente podendo, ao longo da vida, predispor o indivíduo às doenças crônicas, como a hipertrofia cardíaca. Objetivo: O objetivo deste estudo foi analisar o impacto da EPA em relação ao metabolismo celular e sobrevivência de cardiomiócitos, analisando a expressão de RNA mensageiro. Materiais e Métodos: Utilizando camundongos isogênicos C57Bl/6 expostos ao álcool durante a gestação, na proporção 10% (v/v), diluídos em água de consumo, analisamos a expressão de genes participantes das vias de transdução de sinal relacionadas à angiogênese e metabolismo celular em amostras de ventrículo esquerdo (LV) por qPCR. Resultados: Identificamos alterações significativas na expressão de todos os 9 genes analisados no grupo EPA, com redução de 66,4% na expressão de RNAm do fator de crescimento endotelial vascular (VEGF) e aumento de 154,45% de RNAm do gene da proteína desacopladora 2 (UCP2) em relação ao controle. Conclusão: Assim, concluímos que a agressão mediada pelo álcool no miocárdio dos animais do grupo EPA pode modular vias de angiogênese e metabolismo celular. Palavras-chave: exposição pré-natal ao álcool; expressão gênica; coração; transdução de sinal; UCP-2; angiogênese.

IntroductionThe process of cardiac remodeling is characterized by changes in geometry, volume, mass and constitution of the heart in response to tissue aggression. Myocardial hypertrophy is an important component of cardiac remodeling, which allows the heart to maintain its basic functions under increasing load conditions. The renin‐angiotensin system plays an important role in the pathophysiology of myocardial infarction and cardiac hypertrophy and contributes to the progression of heart failure.ObjectiveTo evaluate the effect of photobiomodulation in genes participating in the cardiac hypertrophy process, by the analysis of Edn1, Ace, Agtr1a and Ace2 mRNA.Materials and MethodsFifteen female Wistar rats were divided into three groups: Sham (5), IM (5) and IM + Laser (5) (Ethics Committee: 0015–2012). The infarction induction was made by occlusion of the descending left coronary artery, the laser being applied for 60 seconds at the occlusion site immediately after the infarction. Left ventricle samples from the experimental animals were collected 72h after infarction. Modifications of the gene expression of the genes: Edn1, Ace, Agtr1a and Ace2 were analyzed by Real‐Time PCR.ResultsThe IM group determined a significant increase in expression of the genes: Edn1, Ace and Agtr1a when compared to the Sham group 3 days after the infarction. Laser therapy significantly reduced the expression of these genes when compared to the IM group: Edn1, Ace and Agtr1a when compared to the IM group, suggesting a reduction in hypertrophic processes after laser therapy.ConclusionIncreased ACE expression in experimental models of myocardial infarction, as well as increased endothelin, are related to hypertrophic processes after myocardial infarction. Our studies suggest the action of the laser in the infarcted myocardium through the participation of the renin angiotensin system with the reduction of the expression of the genes involved in these processes.Support or Funding InformationFAPESP, CNPq, CAPES, UNINOVEThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.