The epicardium is a single layer of epithelial (mesothelial) cells that covers the entire heart surface, but whose function in adult mammals is poorly understood. Defining the role of epicardial cells during homeostasis, growth and injury has potential to provide new treatment strategies for human diseases that result in heart failure, due to extensive loss of viable cardiac tissue. We hypothesized that epicardial cells contribute to repair as transplantable progenitor cells for cellular regeneration and as a source of secreted growth factors for cell protection after myocardial infarction. Adult epicardial cells were prospectively isolated as uncommitted epithelial cells using epithelial-specific beta-4 integrin (CD104). These cells underwent epithelial to mesenchymal transformation in culture to generate epicardial cell derivatives (EPDCs). We demonstrate that the C-terminal peptide from Connective Tissue Growth Factor (CTGF-D4), when combined with insulin, effectively primes EPDCs for robust cardiac engraftment in rats and contributes to improvement in cardiac function at one month after MI. Furthermore, we define a signaling axis comprised of CTGF-D4, low density lipoprotein receptor-related protein 6 (LRP6), sex determining region Y-box 9 (Sox9) and Endothelin Receptor B (ETBR) that controls several key processes that impact EPDC graft success: cell survival, proliferation and migration. Interestingly, conditional deletion of ETBR using epicardial-specific transgenic mice prevented epicardial cell proliferation and migration into myocardium after MI. We therefore observed a congruence in the signals and signaling pathways that control the proliferation and migration of endogenous EPDCs after MI and EPDCs that can be generated in cell culture and grafted back to the heart. To gain additional insight into the cellular contribution of the epicardium, we utilized a non-injurious running exercise model to evaluate epicardial activity as a consequence of cardiac hypertrophy (i.e. myocardial growth model). We employed an inducible lineage-tracing system to specifically label and track epicardial cells by GFP expression. Prolonged exercise resulted in a significant number of GFP-positive proliferating epicardial cells and epicardial-derived GFP-positive endothelial cells and few GFP-positive smooth muscle cells in the heart. These observations highlight the cellular plasticity of the adult epicardium and its function as a cardiac progenitor cell niche, maintaining a source of replacement cells. To investigate the paracrine properties of adult epicardial cells for their role in cell protection after MI and reperfusion, human epicardial cells were isolated from donor atrial tissue explants. We predicted that medium conditioned by cultured epicardial cells (EPI CdM) contained secreted reparative factors that would promote endothelial cell survival. Administration of EPI CdM promoted endothelial cell survival in culture and in vivo, 24 hours after ischemia-reperfusion injury. By screening EPI CdM, we detected protein complexes containing hepatocyte growth factor (HGF) with polyclonal IgG that imparted vascular protection in vivo in a manner similar to EPI CdM. Overall, the studies presented here illustrate the unique biology of epicardial cells, their signaling networks, and their contribution to cardiac cell protection and regeneration. Importantly, these properties have the potential to be exploited in translational applications for cardiac repair.

Several studies have shown cellular replacement therapy as a treatment strategy of myocardial infarction but results have been limited. Therefore, enhancing the therapeutic potential of stem cells injected into ischemic microenvironments by novel preconditioning (PC) techniques is critical for improving cellular therapy. Recent studies have shown that inhibition of phosphodiesterase-5 (PDE-5) is a powerful strategy to precondition the heart and cardiomyocytes against ischemia/reperfusion injury. We therefore tested the hypothesis that inhibition of PDE-5 with sildenafil (Viagra®) or selective knockdown with a silencing vector in adipose derived stem cells (ASCs) would improve their survival after ischemia/reoxygenation in vitro and enhance cardiac function following myocardial implantation in vivo. ASCs were treated with sildenafil or infected with PDE-5 silencing vector shRNA (shRNAPDE-5). The cells were subjected to simulated ischemia (SI) and reoxygenation (RO). Both sildenafil and shRNAPDE-5 significantly reduced cell injury, as shown by improved viability, decreased lactate dehydrogenase, and apoptosis. The preconditioned ASCs also demonstrated an increase in the release of growth factors including VEGF, b-FGF, and IGF. The protective effect against SI/RO injury was abolished by inhibition of protein kinase G (PKG) using both a pharmacological inhibitor and selective knockdown with shRNAPKG1α suggesting a PKG-mediated mechanism. To show the effect of preconditioned ASCs in vivo, adult male CD-1 mice underwent myocardial infarction (MI) by occlusion of the left descending coronary artery, followed by direct injection of PBS (control), non-preconditioned ASCs, or preconditioned ASCs (4x105) ASCs into the left ventricle (LV). Preconditioned ASC-treated hearts showed consistently superior cardiac function by all measures as compared with PBS and non-preconditioned ASCs after 4 weeks of treatment. Post-mortem histological analysis demonstrated that preconditioned ASC-treated mice had significantly reduced fibrosis, increased vascular density and reduced resident myocyte apoptosis as compared to mice receiving non-preconditioned ASCs or PBS. VEGF, b-FGF, and Ang-1 were also significantly elevated 4 weeks after cell therapy with preconditioned ASCs. Our data suggests that genetic or pharmacological inhibition of PDE-5 is a powerful new approach to improve stem cell therapy following myocardial infarction.

Administration of small interfering RNA (siRNA) specific for prolyl-4 hydroxylase-2 (PHD2) results in PHD2 inhibition, Hypoxia Inducible Factor-I (HIF-1) activation, and cardioprotection versus Ischemia Reperfusion (IR). This study observes the effects of siRNA-mediated PHD2 inhibition on the distribution of cardioprotective proteins by immunofluorescence and basic histology. Fifteen mice were divided into 5 groups: PHD2 Control, Non-Targeting scramble (NTS) Control, IR Control, PHD2 IR, and NTS IR. Histologically, tissue damage was reduced dramatically in the PHD2 IR group compared to the NTS IR and IR control groups. From confocal images, total fluorescent pixels and intensities were quantified. The PHD2 IR group yielded the highest pixel quantity and intensity for HIF-1 and possessed increased pixels and intensity for Inducible Nitric Oxide Synthase, another cardioprotective protein. These results further demonstrate the cardioprotection and HIF-1 activation conferred by PHD2 siRNA administration and supports its role as a potential therapy to alleviate cardiac IR injury.

L'infarctus du myocarde (IDM) est l'une des principales causes de morbi-mortalité dans le monde et ce malgré une revascularisation rapide de l’artère coronaire occlue. L'obésité est un facteur de risque majeur pour l’IDM, et concerne 15 % de la population française (enquête ObEpi-Roche/INSERM, 2012). L'objectif de notre étude a été d'étudier l'efficacité de stratégies cardioprotectrices comme l’exercice physique chronique ou l’administration d’un donneur de CO (CORM-3) dans un contexte d’obésité. Un effet cardioprotecteur de l'exercice physique chronique a été démontré sur un modèle d’ischémie-reperfusion chez la souris ob/ob (génétiquement dépourvu en leptine). Cet effet implique l’activation de la voie de signalisation cardioprotectrice RISK associée à une diminution des taux cytosoliques des protéines phosphatases inhibitrices correspondantes PTEN et MK3P ce qui aboutit à une amélioration des fonctions mitochondriales. Ce travail montre la capacité différentielle de stratégies à réduire la taille de l’infarctus en cas d’obésité. Par ailleurs, il souligne l’importance du rôle des mécanismes HCO3- dépendants dans le contrôle du pH intracellulaire à la reperfusion. Ils pourraient représenter une étape clef dans la cardioprotection. / Myocardial infarction (MI) remains the leading cause of morbidity and mortality in the developing countries despite significant therapeutic advances over the last years. Obesity is a major risk factor for coronary heart disease and concern 15% of the French population (ObEpi-Roche/INSERM survey, 2012). The aim of our studie was to investigate the efficacy of cardioprotective strategies such as regular treadmill exercice or CO donor administration (CORM-3) against MI during obesity. In ob/ob mice, regular exercise induces a robust cardioprotection by increasing kinase phosphorylation of RISK pathway, decreasing levels of corresponding phosphatases and improving the resistance of mitochondrial permeability transition pore opening. The present study shows differential capabilities of cardioprotective strategies at reducing myocardial infarct size with obesity. In addition, it underlines the role of HCO3- dependent mechanisms in the control of intracellular pH at reperfusion. They could represent a key step for mediating cardioprotection.

Master of Science / Department of Kinesiology / Timothy I. Musch / Both cardiac and peripheral vasculature dysfunction likely contribute, in part, to elevations in TNF-[alpha] and exercise intolerance in chronic heart failure (CHF). The pharmaceutical TNF-[alpha] synthesis suppressor pentoxifylline (PTX) reduces plasma [TNF-[alpha]] and improves left ventricular (LV) function in CHF rats, but the effects of PTX on skeletal muscle blood flow (BF) and vascular conductance (VC) during exercise are unknown. We tested the hypothesis that PTX would elevate skeletal muscle BF and VC at rest and during submaximal treadmill exercise in CHF rats (coronary artery ligation). CHF rats received i.p. injections of 30 mg·kg[superscript]-[superscript]1·day[superscript]-[superscript]1 of PTX (CHF+PTX, n=13) or saline (CHF, n=8) for 21 days. Mean arterial pressure (MAP) and BF (radiolabeled microsphere infusions) were measured at rest and during treadmill exercise (20 m/min, 5% grade). Myocardial infarct (MI) size was not different between groups (CHF: 37±4, CHF+PTX: 37±3% of LV wall; p>0.05). Resting and exercising MAP was greater in CHF+PTX compared to CHF (p<0.05 for both). At rest, total hindlimb skeletal muscle BF and VC were not different between groups (p>0.05). However, during exercise PTX increased total hindlimb BF (CHF: 83±9, CHF+PTX: 114±8 ml·min[superscript]-[superscript]1·100g[superscript]-[superscript]1, p<0.05) and VC (CHF: 0.75±0.08, CHF+PTX: 0.88±0.06 ml·min[superscript]-[superscript]1·100g[superscript]-[superscript]1·mmHg[superscript]-[superscript]1, p<0.05). Furthermore, exercising BF was increased in 21, and VC in 11, of the 28 individual hindlimb muscles or muscle parts with no apparent fiber-type specificity. Thus, PTX administration augments skeletal muscle BF and VC during locomotory exercise in CHF rats, which carries important therapeutic implications for CHF patients.

No description available.

Orientador: Silméia Garcia Zanati Bazan / Resumo: Introdução: A doença arterial coronariana é a primeira causa isolada de morte e responsável por elevado número de hospitalizações em todo o mundo. O desenvolvimento de remodelação ventricular está associado com pior prognóstico após o infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMCST), representando fator de risco para a disfunção ventricular e insuficiência cardíaca. Objetivos: Identificar quais variáveis são preditoras da remodelação ventricular após o IAMCST e avaliar as características clínicas, laboratoriais e ecocardiográficas em pacientes na fase aguda do IAMCST de parede anterior submetidos à angioplastia primária e após seis meses do infarto. Metodologia: Foi realizado um estudo prospectivo, observacional e longitudinal, composto por pacientes com diagnóstico de IAMCST de parede anterior admitidos na Unidade Coronariana (UCO) do Hospital das Clínicas da Faculdade de Medicina de Botucatu no período de julho de 2017 a agosto de 2018. Foram incluídos 50 pacientes, sendo que quatro perderam o seguimento em seis meses e cinco evoluíram a óbito no mesmo período. Durante o período da internação na UCO, os pacientes foram avaliados diariamente e submetidos ao primeiro ecocardiograma em 2 a 3 dias após o IAMCST. No sexto mês após o IAMCST, os pacientes foram submetidos à reavaliação clínica e a novo ecocardiograma, conforme protocolo do serviço. A remodelação cardíaca foi considerada como aumento no volume diastólico superior a 15%. Análise estatística... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Coronary arterial disease is the first isolated death cause and is responsible for an elevated number of hospitalizations all over the world. The development of ventricular remodeling is associated with worse prognosis after ST segment elevation myocardial infarction (STEMI), representing a risk factor for ventricular dysfunction and heart failure. Objectives: To identify which variables are predictors of ventricular remodeling after STEMI and to evaluate clinical, laboratorial and echocardiographic characteristics of patients early post anterior STEMI who went through primary percutaneous intervention and six month after infarction. Methods: This was a prospective, observational and longitudinal study, with anterior STEMI patients admitted to the coronary care unit (CCU) of the Botucatu Medical School Clinics Hospital within July 2017 and August 2018. A total of 50 patients were included, four lost follow-up in six months and five died within the same period. During CCU stay, patients were daily evaluated and submitted to an echocardiogram within the first three days after STEMI. After six months, patients were submitted to a new clinical evaluation and a new echocardiogram, according to local protocol. Ventricular remodeling was considered as a raise in diastolic volume greater than 15%. Statistical analysis: continuous variable both normal and non-normal distribution were presented in either average and standard deviation or median and 25 and 75 percentiles, ... (Complete abstract click electronic access below) / Mestre

Orientador: Sonia Marta Moriguchi / Resumo: Introdução: A doença falciforme (DF) é a doença monogênica herdada mais comum no mundo. Acometimentos cardiopulmonares de caráter progressivo associados à vaso oclusão e fenômenos embólicos assim como, as exacerbações de sintomas respiratórios são causas recorrentes de internações nessa população. A cintilografia de perfusão é método de imagem sensível e consagrado para avaliação hipoperfusão pulmonar, notadamente em processos embólicos. A semi-quantiticação da porcentagem de obstrução vascular de perfusão (POVF) apresenta relação segura com a angiografia. Objetivo: 1) Verificar a correlação entre os sintomas clínicos (Classes funcionais) versus Porcentagem de defeitos perfusionais (POVF%) em portadores de DF e 2) Verificar a associação entre POVF% e espirometria, avaliada pela porcentagem da capacidade vital forçada do predito (CVF%). Casuística e Metodologia Trata-se de estudo transversal observacional descritivo de 22 portadores de Doença Falciforme (DF), com coleta retrospectiva de dados clínicos e de espirometria, no período de 2017-2019 e semi-quantificação da cintilografia de perfusão pulmonar (POVF%), CF de I a IV e CVF% Análise estatística descritiva e inferenciais (Coeficiente de correlação – CC), com nível de significância com p<0,05. Resultados: Foram observados cinco subtipos de DF: SS (n=13), BSB0 (n=04), SS+alfatalassemia (n=02), SS+ fetal elevada (n=02) e SC (n=1). A cintilografia de perfusão pulmonar foi sensível identificando defeitos perfusionais em 91% da ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: INTRODUCITON: Sickle cell disease (SCD) is the most common inherited monogenic disease in the world. Cardiopulmonary complications of a progressive character, associated with vessel occlusion and embolic phenomena, such as, exacerbations of respiratory symptoms are recurrent causes of hospitalization in this population. Perfusion scintigraphy is a sensitive and conspicuous imaging method for evaluating pulmonary hypoperfusion, especially in embolic processes. The semi-quantification of the percentage of vascular perfusion obstruction (POVF) presents a safe relationship with angiography. Objective: 1) To verify the correlation between clinical symptoms (functional classes- FC) versus percentage of perfusion defects (POVF%) in patients with CSD and 2) to verify the association between POVF% and spirometry, evaluated by the percentage of forced vital capacity predicted VCF%). MATERIALS AND METHODOLOGY This was a descriptive, observational cross-sectional study of 22 patients with SCD, with retrospective collection of clinical data and spirometry data for the period 2017-2019 and semi-quantification of pulmonary perfusion scintigraphy (POVF%) , FC from I to IV and VCF% Descriptive and inferential statistical analysis (Coefficient of correlation - CC), with level of significance with p <0.05. Results: Five subtypes of SCD: SS (n = 13), BSB0 (n = 04), SS + alphatassemia (n = 02), high fetal SS + (n = 02) and SC (n = 1) were observed. Pulmonary perfusion scintigraphy was sensitive b... (Complete abstract click electronic access below) / Mestre

O presente estudo procurou avaliar, prospectivamente, a segurança do sistema de tele-eletrocardiografia para a liberação de pacientes que se apresentem a postos de saúde com queixa de dor torácica. Avaliamos a incidência de infarto do miocárdio dessa população ao longo de seis meses. Como objetivo secundário, correlacionamos, retrospectivamente, a razão das probabilidades entre diferentes indicadores clínicos e eletrocardiográficos e a ocorrência do infarto do miocárdio. Entre junho e dezembro de 2006, 32444 pacientes foram atendidos em postos de saúde pública, carentes de cardiologistas e tiveram o seu tele-eletrocardiograma transmitido até uma central de telemedicina, através de linha telefônica fixa. Selecionaram-se 1535 pacientes atendidos devido a dor torácica, que tinham mais de 50 anos e apresentavam exame clínico, laboratorial (troponina I ou creatino fosfoquinase fração MB-CKMB) e tele-eletrocardiográfico normais além de consentirem em repetir o tele-eletrocardiograma após um e seis meses. Todos os pacientes foram seguidos durante seis meses. Não houve eventos durante o primeiro mês. No segundo mês houve 12(0,8%) infartos; no terceiro mês, 18(1,2%); no quarto mês, 38(2,4%) e no sexto, 18(1,2%). Ao longo dos seis meses houve 15(1%) óbitos, sendo 9(0,6%) de origem cardíaca; 9 (0,6%)acidentes vasculares encefálicos e 86(5,6%) infartos agudos do miocárdio. Entre as variáveis que se correlacionaram, independentemente, com maior chance de infarto agudo do miocárdio, encontrou-se a obesidade grau I [p=0,009 RC 4,5 IC 95%(1,5-13,8)], a dislipidemia [p< 0,0001 RC 3,4 IC 95%(2,0-5,8)], a baixa amplitude da onda T em V2 [p<0,001 RC 2,9 IC 95%(2,4-3,5)] e o sobrepeso [p=0,019 RC 2,6 IC 95%(1,2-5,7)]. Cada 0,5mm de redução na amplitude da onda T aumentou em quase três vezes a chance de ocorrência do infarto agudo do miocárdio durante seis meses. O tabagismo apresentou forte tendência [p=0,057 RC 1,7 IC 95%(1,0-2,8)] à regressão logística binária e foi significante após análise por árvore de decisão. Estes resultados permitiram as seguintes conclusões: o sistema de tele-eletrocardiografia oferece alta segurança ao estratificar o risco de pacientes com exame clínico, laboratorial e tele-eletrocardiográfico normais, queixando-se de dor torácica. Identificou-se, ao longo dos seis meses, a população de maior chance de apresentar o evento através de variáveis clínicas (obesidade, dislipidemia, tabagismo e sobrepeso) e tele-eletrocardiográficas (amplitude da onda T em V2), que determinaram, independentemente, a ocorrência de infarto agudo do miocárdio / The present study aimed at prospectively evaluating the reliability of teleeletrocardiography for the discharge of chest pain patients who present themselves at remote medical centers. The incidence of acute myocardial infarction among this population was evaluated during a period of six months. As a secondary objective, the correlation between different clinical and electrocardiographic features and the occurrence of myocardial infarction was retrospectively checked. Between June and December of 2006, 32.444 patients were treated in public medical centers which lacked the assistance of cardiologists. Those patients had their electrocardiogram transmitted to a telemedicine center over a fixed-wired telephone line. Among them 1535 patients who had been assisted due to chest pain were selected. Those patients were all older than 50 years and showed normal clinical and laboratorial (troponine I or creatine phosphokinase MB-CKMB fraction) exams, as well as normal tele-electrocardiograms. They also agreed to repeat the teleelectrocardiogram in a six-month period. All patients were followed up to the sixth-month. In the second month, there were 12 (0,8%) infarctions; in the third month there were 18 (1,2%) infarctions; in the fourth month there were 38 (2,4%) infarctions, and in the sixth month there were 18 (1,2%) infarctions. Over that six month period, there were 15 (1%) deaths, 9 (0,6%) of which were related to cardiac causes; 9 (0,6%) strokes, and 86 (5,6%) acute myocardial infarctions. Among the variables which independently correlated with greater risk of acute myocardial infarction, we found grade I obesity [p=0,009 RC 4,5 IC95%(1,5-13,8)]; dyslipidemia [p<0,0001 RC 3,4 IC 95%(2,0-5,8)]; low T-wave amplitude in V2 [p<0,001 RC 2,9 IC 95%(2,4-3,5)], and overweight [p=0,019 RC 2,6 IC 95%(1,2-5,7)]. Each 0,5mm reduction in the T-wave raised almost three times the chance for the occurrence of acute myocardial infarction in a sixmonth period. Smoking showed a strong tendency [p=0,057 RC 1,7 IC 95%(1,0-2,8)] to binary logistic regression and was significant after decision tree analysis. These results lead to the following conclusions: the teleelectrocardiographic system offers high level of safety and reliability due to its capacity to stratify chest pain patient risk. Over these six months the study identified the population who showed greater chances of presenting the event through clinical (obesity, dyslipidemia, smoking and overweight) and teleelectrocardiography (amplitude of T-wave in V2) variables, which independently, determined the occurrence of acute myocardial infarction

O infarto do miocárdio (IM) é uma patologia causada pela obstrução parcial ou total das artérias coronárias responsáveis pela irrigação do miocárdio. Sabe-se que logo após o IM, o treinamento físico (TF) promove melhora e adaptações benéficas ao sistema cardiovascular. O objetivo do presente estudo foi traçar o perfil de microRNAs na área remanescente ao IM de ratos submetidos ou não ao TF através da técnica de microarray, selecionar e confirmar a expressão de um microRNA específico, por programas de bioinformática que tenha alvos que possam estar envolvidos com a melhora da função cardíaca com o TF. Também foi objetivo deste estudo, verificar a expressão do microRNA-1, do microRNA-29 e do microRNA-214 e dos respectivos alvos destes microRNAs, como o colágeno, NCX e SERCA2a. Para isso, ratos Wistar foram divididos em quatro grupos: SEDENTÁRIO SHAM (SED-SHAM), SEDENTÁRIO INFARTADO (SED-IM), TREINADO SHAM (TR-SHAM) e TREINADO INFARTADO (TR-IM). A função ventricular foi acompanhada com ecocardiografia antes e após oito semanas do protocolo de TF de natação. Os animais foram sacrificados, o RNA foi extraído e posteriormente foi traçado o perfil de microRNAs. Para seleção dos microRNAs foram estipulados dois padrões de expressão entre os grupos. De acordo com os critérios aplicados foram observados, apenas 6 microRNAs para o primeiro padrão de expressão e 3 microRNAs para o segundo padrão de expressão que satisfizeram todos os critérios. O microRNA-339-5p foi escolhido por apresentar expressão diferencial pronunciada como efeito do TF por ter dois genes (alvos selecionados por programas de bioinformática TargetScan, Miranda e PicTar), o Myo1c e o PGC-1 ?, que estão envolvidos com a regulação da função cardíaca. Neste estudo, foi possível verificar que nos grupos TR-SHAM e TR-IM ocorreu aumento da expressão da Myo1c e redução da expressão do microRNA-339-5p. Nossos resultados também mostraram que o TF induziu aumento na expressão dos microRNAs-29a/c, o que está relacionado com significativa diminuição na expressão gênica do COLIAI, COLIIIAI, diminuição na concentração de hidroxiprolina e fração volumétrica de colágeno de ratos com IM. Outro resultado deste estudo é que o TF induziu diminuição na expressão dos microRNAs-1 e 214, o que está relacionado com aumento na expressão protéica dos alvos SERCA-2a e NCX de ratos com IM. Esses efeitos estão associados com a melhora da função ventricular avaliada pela FEAT% (função sistólica) e pela relação E/A (função diastólica), realizado por avaliação ecocardiográfica após o período de TF. / Myocardial infarction (MI) is a disease caused by partial or total blockage of the myocardial coronary arteries. It is known that after MI, physical training (PT) improves and promotes beneficial adaptations to the cardiovascular system. The aim of this study was to analyse the microRNAs profile in the remaining area to MI in rats submitted to PT by microarray and select a specific microRNA by bioinformatics software that has targets involved with the improvement of cardiac function by PT. Also, the aim of this study was to verify the expression of the microRNA-1, microRNA-29 and microRNA-214 and its targets, such as collagen, NCX and SERCA2a. For this, rats were divided into four groups: SEDENTARY SHAM (SHAM - SED), INFARCTED SEDENTARY (SED-MI), TRAINED SHAM (TR-SHAM) and INFARCTED TRAINED (TR-IM). Ventricular function was monitored with echocardiography before and after eight weeks of the PT. The animals were sacrificed, the RNA was extracted and traced the profile of microRNAs. For selection of microRNAs were stipulated two patterns of expression between the groups. The first standard, 6 microRNAs were selected and in the second standard, 3 microRNAs were selected to satisfy all criteria. The microRNA- 339-5p was chosen because of pronounced differential expression with PT and have two target genes selected by bioinformatics programs (TargetScan, Miranda and PicTar) Myo1c and the PGC-1 ? are involved in the regulation of cardiac function. In this study, we found that the SHAM group and the group with MI undergoing PT increased expression of Myo1c in contrast to a decreased expression of microRNA-339- 5p. Our results also showed that PT induced increased expression of microRNA-29a/c, which is associated with a significant decrease in gene expression of COLIAI, COLIIIAI, the hydroxyproline xvii concentration and collagen volume fraction of rats with MI. Another result of this study is that the PT induced decrease in the expression of microRNA-1 and microRNA-214, which is related to the increase in protein expression of the targets SERCA-2a and NCX of rats with MI. These effects are associated with improved ventricular function assessed by FEAT % (systolic function) and E/A ratio (diastolic function), performed by echocardiography after the period of PT