La inhibición de Rho quinasa post infarto mejora el remodelado y la función ventricular: mecanismos involucrados a nivel preclínico / Rho-kinase inhibition post myocardial infarction improves remodeling and systolic function: a preclinical study of intervening factors in a pre-clinical study

Resumen: Objetivo: Determinar algunos mecanismos moleculares por los cuales la activación de ROCK cardíaca post infarto del miocardio (IAM) participa en el remodelado y en deterioro de la función sistólica. Métodos: Determinación simultánea de niveles de proteínas blanco de ROCK cardíaca, de función sistólica in vivo del ventrículo izquierdo (VI) y de fibrosis e hipertrofia cardíaca en ratas con IAM en condiciones de inhibición de ROCK con fasudil. Resultados : Siete días post IAM la masa ventricular relativa aumentó significativamente en un 30% en el grupo MI y se redujo con fasudil. La disfunción sistólica VI mejoró significativamente con fasudil mientras que la activación de ROCK cardíaca se redujo a niveles del grupo control. El inhibidor de ROCK también redujo significativamente los niveles cardíacos elevados de las isoformas ROCK1 y ROCK2, de MHC-β y del colágeno miocárdico. En el grupo con IAM aumentaron significativamente los niveles de fosforilación de ERK 42 y ERK 44 (en 2 veces y en 63%, respectivamente), mientras que en el grupo IAM tratado con fasudil estos niveles fueron similares a los del grupo control. El IAM aumentó significativamente los niveles fosforilados del factor de transcripción GATA-4, que se normalizaron con el inhibidor de ROCK. Conclusiones: La disfunción sistólica post IAM se asoció fuertemente con la activación del ROCK cardíaca y con la fosforilación de proteínas río abajo de ROCK que promueven remodelado cardíaco como β-MHC y la vía ERK / GATA-4.

Abstracts: Objective: to determine some molecular mechanisms by which cardiac ROCK activation after myocardial infarction (MI) intervene in cardiac systolic function decline and remodeling. Methods: simultaneous measurement of different cardiac ROCK target proteins levels, in vivo left ventricular (LV) systolic function, myocardial fibrosis, and hypertrophy in rats with MI under ROCK inhibition with fasudil were performed. Results: seven days after MI the relative ventricular mass increased significantly by 30% in the MI groupand was reduced with fasudil. LV systolic dysfunction improved significantly with fasudil whereas at the same time cardiac ROCK activation was reduced to sham levels. The ROCK inhibitor also reduced increased cardiac levels of both ROCK1 and ROCK2 isoforms, β-MHC levels and myocardial collagen volume fraction decline. MI significantly increased phosphorylation levels of ERK 42 and ERK 44 by 2-fold and 63% respectively whereas in the fasudil-treated MI group these levels were similar to those in the sham group. MI significantly increased phosphorylated levels of the transcription factor GATA-4 which were normalyzed by the ROCK inhibitor. Conclusion: LV systolic dysfunction after MI was strongly associated to cardiac ROCK activation and subsequent phosphorylation of ROCK target proteins that promote ventricular remodeling, such as β-MHC and the ERK/GATA-4 pathway. ROCK inhibition with fasudil significantly improved systolic function, diminished myocardial fibrosis, and normalized β-MHC and ERK/GATA-4 phosphorylation levels.

Envelhecimento dos produtores no meio rural na região do Alto Jacuí/RS e consequente migração para cidade / Aging of producers in rural areas in the region of high Jacuí/RS and consequential migration

Objetivou-se nesta pesquisa analisar os fatores relacionados com o envelhecimento da população rural na região do Alto Jacuí (RS), que interferem na diminuição do número de residentes do meio rural. O campo empírico do estudo foram os 14 municípios da região do Alto Jacuí, através do recorte espacial metodológico do Conselho Regional de Desenvolvimento – Corede – Alto Jacuí. Através de amostragem por acessibilidade, foram realizadas 171 (cento e setenta e uma) entrevistas, abrangendo produtores que venderam ou arrendaram suas terras e migraram para a cidade, compradores ou arrendatários e Segmentos Rurais. A análise dos dados qualitativos foi realizada pelo método de análise de conteúdo, assim, a descrição dos dados da pesquisa apresentam extratos retirados diretamente das anotações originais. Os resultados da pesquisa indicam que a saída dos idosos aposentados para a cidade do seu município, parece transparecer um processo natural neste modelo de desenvolvimento. Assim, a diferença entre o rural e o urbano, quando se trata da infraestrutura relacionada aos serviços quais necessita o idoso, principalmente os de saúde, faz com que ele busque fora do meio rural esta tranquilidade.

The objective of this study aimed to analyze the factors related to the aging of the rural population in the Upper Jacuí (RS), which interfere with the decreasing number of residents through rural. The empirical setting to the study were the 14 municipal districts from the Cruz Alta region, through the methodological cropping from CORED Alto Jacuí. Through the sample for accessibility, it were fulfilled 171 (one hundred and seventy-one) interviews including producers that sold or rent their properties and migrated to the city, buyers or tenants and Rural Segment. The analysis of the qualitative data was fulfilled by the method of analysis of the content, so, the description of the research data presents extracts directly taken from the original annotations.The results of the research indicate that the output retired elderlies to the city from their municipal district seems imply a natural process in that model of development. Thus, the difference between rural and urban, as it is infrastructure it needs, especially when you need health care, seek out causes of this rural tranquility.