MicroRNAs: new players in heart failure.

MicroRNAs (miRNAs) are a class of non-coding small RNAs representing one of the most exciting areas of modern medical science. miRNAs modulate a large and complex regulatory network of gene expression of the majority of the protein-coding genes. Currently, evidences suggest that miRNAs play a crucial role in the pathogenesis of heart failure. Some miRNAs as miR-1, miR-133 and miR-208a are highly expressed in the heart and strongly associated with the development of cardiac hypertrophy. Recent data indicate that these miRNAs as well as miR-206 change their expression quickly in response to physical activity. The differential regulation of miRNAs in response to exercise suggests a potential value of circulating miRNAs (c-miRNAs) as biomarkers of physiological mediators of the cardiovascular adaptation induced by exercise. Likewise, serum levels of c-miRNAs such as miR-423-5p have been evaluated as potential biomarkers in the diagnosis and prognosis of heart failure. On the other hand, the manipulation of miRNAs levels using techniques such as 'miR mimics' and 'antagomiRs' is becoming evident the enormous potential of miRNAs as promising therapeutic strategies in heart failure.

Determinants of peak VO2 in heart transplant recipients.

OBJECTIVE: To establish the determinants of the peak VO2 in heart transplant recipients. METHODS: Patient's assessment was performed in two consecutive days. In the first day, patients performed the heart rate variability assessment followed by a cardiopulmonary exercise test. In the second day, patients performed a resting echocardiography. Heart transplant recipients were eligible if they were in a stable condition and without any evidence of tissue rejection diagnosed by endomyocardial biopsy. Patients with pacemaker, noncardiovascular functional limitations such as osteoarthritis and chronic obstructive pulmonary disease were excluded from this study. RESULTS: Sixty patients (68% male, 48 years and 64 months following heart transplantation) were assessed. Multivariate analysis selected the following variables: receptor's gender (P=0.001), receptor age (P=0.049), receptor Body Mass Index (P=0.005), heart rate reserve (P <0.0001), left atrium diameter (P=0.016). Multivariate analysis showed r=0.77 and r2=0.6 with P <0.001. Equation: peakVO2=32.851 - 3.708 (receptor gender) - 0.067 (receptor age) - 0.318 (receptor BMI) + 0.145 (heart rate reserve) - 0.111 (left atrium diameter). CONCLUSION: The determinants of the peak VO2 in heart transplant recipients were: receptor sex, age, Body Mass Index, heart rate reserve and left atrium diameter. Heart rate reserve was the unique variable positively associated with peak VO2. This data suggest the importance of the sympathetic reinnervation in peak VO2 in heart transplant recipients.

The emerging role of miR-208a in the heart.

MicroRNAs (miRNAs) are a class of regulatory small RNAs that have fundamentally transformed our understanding of how gene networks are regulated representing one of the most exciting areas of the modern cardiology research. Among all known miRNAs, miR-208a is one of the most important heart-enriched miRNA playing a crucial role in the heart health and disease. miR-208a is a member of a miRNA family that also included miR-208b and is encoded by an intronic region of the Myh6 gene. Within the heart, miR-208a and miR-208b are involved in the regulation of the myosin heavy chain isoformswitch during development and in pathophysiological conditions. miR-208a is sufficient to induce arrhythmias, cardiac remodeling, and to regulate the expression of hypertrophy pathway components and the cardiac conduction system. Recently, the identification of miR-208a in the bloodstream has led to a great clinical interest to use this molecule as a potential noninvasive biomarker of myocardial injuries.

Exercise capacity in early and late adult heart transplant recipients.

BACKGROUND: The aim of this study was to compare peak oxygen consumption (VO(2)), heart rate (HR) reserve and HR recovery in early and late heart transplant recipients. Moreover, we also aimed to correlate peak VO(2) and HR reserve. METHODS: Fivteen heart transplant recipients (8 early and 7 late), 8 ± 3 and 161 ± 58 months after transplantation, respectively, performed a cardiopulmonary exercise test. RESULTS: Early heart transplant recipients showed lower HR reserve compared to late heart transplant recipients, 39 ± 15 vs. 58 ± 19 bpm (p = 0.049), respectively. Peak VO(2) (23.4 ± 4 vs. 21.8 ± 5 mL/kg/min, p = 0.56), VO(2) respiratory compensation point (18.7 ± 2 vs. 18.5 ± 4 mL/ /kg/min, p = 0.48) and time of exercise testing (14 ± 3 vs. 13 ± 3 min, p = 0.95) %age- -predicted peakVO(2) (65 ± 12 vs. 70 ± 10%, p = 0.24) were not different between the groups. Moreover, peak VO2 and %age-predicted peakVO(2) correlated with HR reserve only in early heart transplant recipients (r = 0.89, p = 0.003 and r = 0.71, p = 0.04, respectively). Early heart transplant recipients increased HR (2.5 ± 2.0% at fi rst minute and 0.7 ± 2.3% at the second minute), while late recipients decreased HR (-6.0 ± 4.7 at fi rst minute and -15.5 ± 2.4 at the second minute) at the recovery period of cardiopulmonary exercise test. CONCLUSIONS: Exercise capacity did not show difference between early and late heart transplant recipients. HR reserve was higher in late compared to early recipients. HR reserve only correlated with peak VO(2) in early recipients. Moreover, only late heart transplant recipients showed decrease in HR during the recovery period of cardiopulmonary exercise test.

The new mutation L321F in Candida albicans ERG11 gene may be associated with fluconazole resistance.

BACKGROUND: For many years fluconazole has been commonly used to treat Candida infections. However, the indiscriminate use of this antimycotic therapy has favored the emergence of resistant isolates. Mutations in the ERG11 gene have been described as one of the primary mechanisms of resistance in Candida species. AIMS: In this study we investigated missense mutations in ERG11 genes of Candida albicans, Candida glabrata and Candida tropicalis isolates previously evaluated by susceptibility testing to fluconazole. METHODS: Screening for these mutations was performed on 19 Candida clinical isolates (eight C. albicans, five C. glabrata and six C. tropicalis) resistant and susceptible to fluconazole. The ERG11 gene was amplified by PCR with specific primers for each Candida species and analyzed by automated sequencing. RESULTS: We identified 14 different missense mutations, five of which had not been described previously. Among them, a new mutation L321F was identified in a fluconazole resistant C. albicans isolate and it was analyzed by a theoretical three-dimensional structure of the ERG11p. CONCLUSION: The L321F mutation in C. albicans ERG11 gene may be associated with fluconazole resistance.

MicroRNAs: a new paradigm in the treatment and diagnosis of heart failure?

MicroRNAs (miRNAs) are a group of newly discovered small RNAs, non-coding, which represent one of the most exciting areas of modern medical science as they modulate a huge and complex regulatory network of gene expression. Lines of evidence have recently suggested that miRNAs play a key role in the pathogenesis of heart failure. Some miRNAs highly expressed in the heart, such as miR-1, miR-133 and miR-208, are strongly associated with the development of cardiac hypertrophy, while the exact role of miR-21 in the cardiovascular system remains controversial. Serum levels of circulating miRNAs such as miR-423-5p are being evaluated as potential biomarkers in the diagnosis and prognosis of heart failure. On the other hand, the manipulation of levels of miRNAs using techniques such as mimicking the miRNAs (miRmimics) and antagonistic miRNAs (antagomiRs) is making increasingly evident the enormous potential of miRNAs as promising therapeutic strategies in heart failure.

Determinants of peak VO2 in heart transplant recipients / Determinantes do pico de VO2 em transplantados cardíacos

Objective: To establish the determinants of the peak VO2 in heart transplant recipients. Methods: Patient's assessment was performed in two consecutive days. In the first day, patients performed the heart rate variability assessment followed by a cardiopulmonary exercise test. In the second day, patients performed a resting echocardiography. Heart transplant recipients were eligible if they were in a stable condition and without any evidence of tissue rejection diagnosed by endomyocardial biopsy. Patients with pacemaker, noncardiovascular functional limitations such as osteoarthritis and chronic obstructive pulmonary disease were excluded from this study. Results: Sixty patients (68% male, 48 years and 64 months following heart transplantation) were assessed. Multivariate analysis selected the following variables: receptor's gender (P=0.001), receptor age (P=0.049), receptor Body Mass Index (P=0.005), heart rate reserve (P <0.0001), left atrium diameter (P=0.016). Multivariate analysis showed r=0.77 and r2=0.6 with P <0.001. Equation: peakVO2=32.851 - 3.708 (receptor gender) - 0.067 (receptor age) - 0.318 (receptor BMI) + 0.145 (heart rate reserve) - 0.111 (left atrium diameter). Conclusion: The determinants of the peak VO2 in heart transplant recipients were: receptor sex, age, Body Mass Index, heart rate reserve and left atrium diameter. Heart rate reserve was the unique variable positively associated with peak VO2. This data suggest the importance of the sympathetic reinnervation in peak VO2 in heart transplant recipients. .

Objetivo: Estabelecer os determinantes do VO2 pico em transplantados de coração. Métodos: Avaliação do paciente foi realizada em dois dias consecutivos. No primeiro dia, os pacientes realizaram a avaliação da variabilidade da frequência cardíaca seguida de um teste de esforço cardiopulmonar. No segundo dia, os pacientes realizaram ecocardiografia de repouso. Os transplantados foram elegíveis se estivessem em uma condição estável e sem qualquer evidência de rejeição diagnosticada por biópsia endomiocárdica. Pacientes com marca-passo, limitações funcionais não cardiovasculares, tais como osteoartrite e doença pulmonar obstrutiva crônica foram excluídos deste estudo. Resultados: Sessenta pacientes (68% do sexo masculino, 48 anos e 64 meses após o transplante cardíaco) foram avaliados. A análise multivariada selecionou as seguintes variáveis: sexo (P=0,001), idade (P=0,049), Índice de Massa Corporal (P=0,005), frequência cardíaca de reserva (P <0,0001), diâmetro do átrio esquerdo (P=0,016), variáveis do receptor. A análise multivariada mostrou r=0,77 e r2=0,6, com P <0,001. Equação: VO2=32,851 - 3,708 (sexo receptor) - 0,067 (idade receptor) - 0,318 (IMC receptor) + 0,145 (frequência cardíaca de reserva) - 0,111 (diâmetro de átrio esquerdo). Conclusão: Os determinantes do pico de VO2 em transplantados de coração foram: sexo receptor, idade, Índice de Massa Corporal, frequência cardíaca de reserva e diâmetro do átrio esquerdo. A frequência cardíaca de reserva foi a única variável positivamente associada com o pico de VO2. Estes dados sugerem a importância da reinervação simpática no pico de VO2 em transplantados de coração. .

MicroRNAs: um novo paradigma no tratamento e diagnóstico da insuficiência cardíaca? / MicroRNAs: a new paradigm in the treatment and diagnosis of Heart failure? / MicroRNAs: ¿un nuevo paradigma en el tratamiento y diagnóstico de la insuficiencia cardíaca?

MicroRNAs (miRNAs) são um grupo recém-descoberto de pequenos RNAs, não codificantes, que representam uma das áreas mais estimulantes da ciência médica moderna por modularem uma enorme e complexa rede regulatória da expressão dos genes.Recentemente, linhas de evidências sugerem que os miRNAs desempenham um papel crucial na patogênese da insuficiência cardíaca. Alguns miRNAs altamente expressos no coração como o miR-1, miR-133 e miR-208 estão fortemente associados ao desenvolvimento da hipertrofia cardíaca, enquanto o exato papel de miR-21 no sistema cardiovascular permanece controverso. Os níveis séricos de miRNAs circulantes como o miR-423-5p estão sendo avaliados como potenciais biomarcadores no diagnóstico e prognóstico da insuficiência cardíaca.Por outro lado, a manipulação dos níveis de miRNAs usando técnicas como os mimetizadores de miRNAs (miRmimics) e miRNAs antagônicos(antagomiRs) está tornando cada vez mais evidente o enorme potencial dos miRNAs como promissoras estratégias terapêutica sna insuficiência cardíaca.

MicroRNAs (miRNAs) are a group of newly discovered small RNAs, non-coding, which represent one of the most exciting areas of modern medical science as they modulate a huge and complex regulatory network of gene expression. Lines of evidence have recently suggested that miRNAs play a key role in the pathogenesis of heart failure. Some miRNAs highly expressed in the heart, such as miR-1, miR-133 and miR-208, are strongly associated with the development of cardiac hypertrophy, while the exact role of miR-21 in the cardiovascular system remains controversial. Serum levels of circulating miRNAs such as miR-423-5p are being evaluated as potential biomarkers in the diagnosis and prognosis of heart failure. On the other hand, the manipulation of levels of miRNAs using techniques such as mimicking the miRNAs (miRmimics) and antagonistic miRNAs (antagomiRs) is making increasingly evident the enormous potential of miRNAs as promising therapeutic strategies in heart failure.

MicroRNAs(miRNAs) son un grupo recién descubierto de pequeños RNAs, no codificantes, que representan una de las áreas más estimulantes de la ciencia médica moderna por modular en una enorme y compleja red regulatoria de la expresión de los genes. Recientemente, líneas de evidencias sugieren que los miRNAs desempeñan un papel crucial en la patogénesis de la insuficiencia cardíaca. Algunos miRNAs altamente expresados en el corazón como el miR-1, miR-133 y miR-208 están fuertemente asociados al desarrollo de la hipertrofia cardíaca, mientras que el exacto papel de miR-21 en el sistema cardiovascular permanece controvertido. Los niveles séricos de miRNAs circulantes como el miR-423-5p están siendo evaluados como potenciales biomarcadores en el diagnóstico y pronóstico de la insuficiencia cardíaca. Por otro lado, la manipulación de los niveles de miRNAs usando técnicas como los mimetizadores de miRNAs (miRmimics) y miRNAs antagónicos (antagomiRs) está volviendo cada vez más evidente el enorme potencial de los miRNAs como promisorias estrategias terapéuticas en la insuficiencia cardíaca.

O controle da (El control de la) expressão gênica por microRNAs e sua (y su) importância para a (la) medicina / The control of gene expression by microRNAs and their importance in medicine

MicroRNAs (miRNAs) são um (constituyen un) grupo de pequenos RNAs, com aproximadamente 19-25 nucleotídeos, que não-codificam (no codifican) proteínas e que estão (y se encuentran) presentesem grande parte dos organismos eucariontes, incluindo o homem. Desde a sua descoberta (1993) osmiRNAs vêm ganhando um (vienen ganando un) enorme destaque na (papel destacado en la) comunidade científica, representando hoje uma das (en la actualidad una de las) áreas mais estimulantes da ciência médica moderna. Estas moléculas têm a singular (poseen la singular) habilidade de modular em uma (para modular una) enorme e complexa rede (compleja red) regulatória da expressão dos genes estimada em cerca de 70% do genoma humano. Os miRNAs exercem sua (ejercen su) função por meioda (a través de la) inibição da tradução de mRNAs específicos (controle pós-transcricional), ou seja, impedem a (es decir, impiden la) síntese de determinadas proteínas durante um certo intervalo de tempo.Desta forma, os miRNAs desempenham um papel crucial não só nos (no sólo en los) processos celulares normais, como desenvolvimento e (desarrollo y) diferenciação, mas também na (en la) patogênese de diversas doenças (enfermedades). Estudos recentes mostram que os perfis (los perfiles) de miRNAs se alteram de acordo com a etiologia, intensidade e estágio da (y etapa de la) doença, podendo ser utilizados como potenciais ferramentas de diagnóstico e prognóstico. Aliado a isto, a (Asociado con esto, la) possibilidade do uso dos miRNAs para silenciar ou ativar (o activar) genes específicos é uma (constituye una) atual e promissora ferramenta que permite o desenvolvimento de novas estratégias terapêuticas individualizadas, ou seja (es decir), baseadas na (con base en la) condição específica de cada paciente.Nesta revisão serão abordados aspectos sobre a biologia dos miRNAs e como eles podem nos ajudar no (y como ellos pueden ayudar en el) combate às (de las) enfermidades humanas...