MicroRNA-195 in cardiac aging: Current Issues and Perspectives
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2021-02-24
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[ES]Durante el envejecimiento, el corazón exhibe un deterioro degenerativo asociado a la edad en su estructura y función. El envejecimiento del corazón se caracteriza por una hipertrofia ventricular (VI), una disminución de la función diastólica, una disminución de la capacidad de ejercicio, así como un aumento en la prevalencia de la fibrilación auricular. Esta disfunción asociada a la edad es un criterio importante de morbilidad, mortalidad y deterioro general de la calidad de vida en las personas mayores. A medida que aumenta la población que envejece, es importante identificar los mecanismos responsables de esta enfermedad cardiovascular relacionada con la edad. Aunque los fenotipos del envejecimiento cardíaco se han caracterizado bien, los factores moleculares responsables del envejecimiento no se comprenden completamente, sin embargo, los cambios en la expresión de los genes del factor de crecimiento hipertrófico se han implicado en la hipertrofia del corazón envejecido.
Los microARN (miARN, miR) son pequeñas moléculas de ARN que regulan la expresión génica. Se prevé que cada microARN regule la expresión de hasta varios cientos de genes. La expresión de numerosos microARN y sus genes diana cambia con la edad o en enfermedades. Esto hace que los microARN sean candidatos muy fuertes como dianas terapéuticas para los trastornos relacionados con la edad. En un estudio anterior se ha demostrado que los niveles de microARN-195 cambian in vitro en las células madre mesenquimales aisladas de la médula ósea de ratones de edad en comparación con los ratones jóvenes. Una nueva investigación propone que la abundancia de microARN-195 es un factor importante que contribuye a la enfermedad cardíaca. Sin
embargo, el papel funcional del microARN-195 en el proceso de envejecimiento aún no se comprende y es difícil de alcanzar. Utilizando sistemas de organismos modelo, elegimos realizar ratones deficientes en miR-195b por Crispr / Cas9 para estudiar el potencial de la intervención basada en miRNA-195 para prevenir o retrasar el envejecimiento cardíaco.
El primer objetivo determinará el posible cambio morfológico en el tejido cardíaco de ratones transgénicos viejos en comparación con los ratones controles emparejados de tipo salvaje tratados o no con angiotensina. El segundo objetivo confirmará importantes genes diana de microARN-195 en el corazón y caracterizará los detalles de las interacciones de microARN y los genes específicos que regulan en el contexto de enfermedades cardíacas relacionadas
con el envejecimiento.
Este proyecto es importante para fortalecer nuestro conocimiento sobre la base molecular del microARN-195 en el contexto del envejecimiento cardíaco y es probable que conduzca al diseño de nuevos enfoques terapéuticos para prevenir, retrasar o tratar la atrofia cardíaca relacionada con la edad.
[EN]During aging, heart exhibits a degenerative age-associated decline in structure and function. Aging of heart is characterized by a ventricular (LV) hypertrophy, a decline in diastolic function a decline in exercise capacity, as well as an increase in the prevalence of atrial fibrillation. This age-associated dysfunction is a major criterion of morbidity, mortality, and overall declines of quality of life in the elderly people. As the ageing population increases, it is important to identify the mechanisms responsible for this age-related cardiovascular disease. Although the phenotypes of cardiac aging have been well characterized, the molecular factors responsible for aging are not fully understood, however changes in the expression of hypertrophic growth factor genes have been implicated in hypertrophy of aged heart. MicroRNAs (miRNAs, miRs) are small RNA molecules that regulate gene expression. Each microRNA is predicted to regulate the expression of up to several hundred genes. Expression of numerous microRNAs and their target genes changes with age or in diseases. This makes microRNAs very strong candidates for therapeutic targets for age-related disorders. In previous study it has shown that that the levels of microRNA-195, change in vitro in mesenchymal stem cells isolated from bone marrow of age mice compared to young mice. New research proposes that microRNA-195 abundance are a major contributing factor for heart disease. However the functional role of microRNA-195 in aging process still not understood and elusive. Using model organism systems, we choose to perform miR-195b deficient mice by Crispr/Cas9 to study the potential of miRNA-195 based intervention to prevent or delay heart aging. The first objective will determine the possible morphological change in the heart tissue of old transgenic mice compared with wild type matched controls mice treated or not with angiotensin. The second objective will confirm important microRNA-195 target genes in heart, and characterize the details of the interactions of microRNAs and the specific genes they regulate in the context of aging related heart disease. This present project is important to strengthen our knowledge about the molecular basis of microRNA- 195 in the context of heart aging and is likely to lead to the design of novel therapeutic approaches to prevent, delay or treat age-related heart wasting.
[EN]During aging, heart exhibits a degenerative age-associated decline in structure and function. Aging of heart is characterized by a ventricular (LV) hypertrophy, a decline in diastolic function a decline in exercise capacity, as well as an increase in the prevalence of atrial fibrillation. This age-associated dysfunction is a major criterion of morbidity, mortality, and overall declines of quality of life in the elderly people. As the ageing population increases, it is important to identify the mechanisms responsible for this age-related cardiovascular disease. Although the phenotypes of cardiac aging have been well characterized, the molecular factors responsible for aging are not fully understood, however changes in the expression of hypertrophic growth factor genes have been implicated in hypertrophy of aged heart. MicroRNAs (miRNAs, miRs) are small RNA molecules that regulate gene expression. Each microRNA is predicted to regulate the expression of up to several hundred genes. Expression of numerous microRNAs and their target genes changes with age or in diseases. This makes microRNAs very strong candidates for therapeutic targets for age-related disorders. In previous study it has shown that that the levels of microRNA-195, change in vitro in mesenchymal stem cells isolated from bone marrow of age mice compared to young mice. New research proposes that microRNA-195 abundance are a major contributing factor for heart disease. However the functional role of microRNA-195 in aging process still not understood and elusive. Using model organism systems, we choose to perform miR-195b deficient mice by Crispr/Cas9 to study the potential of miRNA-195 based intervention to prevent or delay heart aging. The first objective will determine the possible morphological change in the heart tissue of old transgenic mice compared with wild type matched controls mice treated or not with angiotensin. The second objective will confirm important microRNA-195 target genes in heart, and characterize the details of the interactions of microRNAs and the specific genes they regulate in the context of aging related heart disease. This present project is important to strengthen our knowledge about the molecular basis of microRNA- 195 in the context of heart aging and is likely to lead to the design of novel therapeutic approaches to prevent, delay or treat age-related heart wasting.