Análisis de la variabilidad en la longitud telomérica de pacientes con enfermedad cardiovascular, sometidos a un programa de ejercicio físico en un centro médico de la ciudad de Barranquilla
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Fecha
2023
Autores
Espinosa Otálora, Raúl Enrique
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Ediciones Universidad Simón Bolívar
Facultad de Ciencias Básicas y Biomédicas
Facultad de Ciencias Básicas y Biomédicas
Resumen
Las Enfermedades cardiovasculares (ECV), son desordenes de origen
multifactorial, que según la Organización Mundial de la Salud (OMS), constituyen la
principal causa de mortalidad en Colombia y a nivel mundial. El desarrollo de estas
patologías se relaciona con diversos factores de riesgo ambientales, metabólicos y
genéticos; entre los factores genéticos, se encuentran biomarcadores con potencial
para predecir el riesgo de ECV. Uno de estos biomarcadores es la longitud de los
telómeros (TL), los cuales son estructuras al extremo del cromosoma, que actúan
como marcador del envejecimiento biológico. Esto se debe a que con el tiempo
reducen su longitud por la división celular, lo que genera inestabilidad cromosómica
y senescencia celular. Además de la división celular, factores como enfermedades
o estilos de vida se han relacionado con cambios en la TL; entre estos, la actividad
física es asociada con efecto protector sobre la TL, siendo también un protocolo
recomendado en pacientes para el tratamiento de ECV. Sin embargo, se desconoce
la relación causa-efecto entre la actividad física, la TL y las ECV. El presente trabajo
se propuso analizar el efecto de un programa de ejercicio sobre la Longitud de
Telómero en pacientes diagnosticados con ECV de la ciudad de Barranquilla. Los
participantes del estudio se seleccionaron teniendo en cuenta los criterios de
inclusión y exclusión, a partir de un listado de pacientes atendidos por enfermedad
cardiovascular. Los pacientes seleccionados se citaron a una valoración por
cardiología, donde se registró la presencia de factores de riesgo cardiovascular
(FRCV), y se realizó toma de una muestra de sangre venosa, para determinar la TL previo intervención. Posteriormente se entregó a cada paciente el protocolo de ejercicio para 3 meses, y al finalizar el protocolo se citó a los participantes a una segunda toma de sangre para determinar la TL post intervención. Las muestras se procesaron por triplicado utilizando la técnica de Reacción en Cadena de la Polimerasa Cuantitativa en tiempo real (qPCR). Para cada muestra se realizó una primera reacción dirigida a telómero y una segunda dirigida al gen 36B4, el cual se utilizó como referencia para determinar el número de copias del genoma por reacción, para cada paciente. Adicionalmente, se determinó una curva de calibración, utilizando diluciones seriadas de oligómeros sintetizados de tamaño conocido de secuencia de telómero y del gen 36B4, para calcular una TL absoluta (aTL). Los datos obtenidos se exportaron y analizaron utilizando los softwares Excel y IBM-SPSS 26.0, utilizando pruebas estadísticas no paramétricas. Los resultados muestran una TL post ejercicio 5,54% más larga que la aTL pre-ejercicio, aunque no se evidenció una diferencia estadísticamente significativa entre las aTL pre y post intervención (p=0,750). Así mismo tampoco se observó una diferencia significativa en la variación de la TL entre los pacientes, respecto a la presencia de FRCV como comorbilidades (p=0,396), perfil de lipídico elevado (0,762), hipertensión arterial (p=0,659) o ECV (p=0,81). Estos resultados sugieren un posible efecto de mantenimiento de la TL debido al programa de ejercicio, independientemente del estado cardiovascular inicial del paciente; sin embargo, teniendo en cuenta que este estudio solo contempló la Actividad física, el efecto observado puede estar influenciado, por factores, como la dieta, los cuales pueden actuar como factores de protección adicional; por tal motivo no es posible relacionar la actividad física con un efecto de mantenimiento del telómero en pacientes con ECV, por lo que se hace necesario realizar un estudio que incluya la supervisión de otras posibles variables que puedan influenciar en la TL.
Cardiovascular diseases (CVD) are multifactorial disorders that, according to the World Health Organization (WHO), are the leading cause of mortality in Colombia and worldwide. The development of these pathologies is related to various environmental, metabolic and genetic risk factors; among the genetic factors, there are biomarkers with the potential to predict the risk of CVD. One of these biomarkers is telomere length (TL), which are structures at the end of the chromosome that function as a marker of biological aging. This is because over time they reduce in length due to cell division, which generates chromosomal instability and cellular senescence. In addition to cell division, factors such as diseases or lifestyles have been related to changes in TL; among these, physical activity is associated with a protective effect on TL, being also a recommended protocol in patients for the treatment of CVD. However, the cause-effect relationship between physical activity, TL and CVD is unknown. The present study aimed to analyze the effect of an exercise program on telomere length in patients diagnosed with CVD in the city of Barranquilla. The study participants were selected considering the inclusion and exclusion criteria, from a list of patients treated for cardiovascular disease. The selected patients were scheduled for a cardiology evaluation, where the presence of cardiovascular risk factors (CVRF) was recorded, and a venous blood sample was taken to determine the pre-intervention TL. Subsequently, each patient was given the exercise protocol for 3 months, and at the end of the protocol, the participants were summoned to a second blood sampling to determine the post-intervention TL. The samples were processed in triplicate using the real-time quantitative polymerase chain reaction (qPCR) technique. For each sample, a first reaction targeting the telomere and a second reaction targeting the 36B4 gene were performed, which was used as a reference to determine the number of genome copies per reaction for each patient. Additionally, a calibration curve was determined, using serial dilutions of synthesized oligomers of known size of telomere sequence and 36B4 gene, to calculate an absolute TL (aTL). The data obtained were exported and analyzed using Excel and IBM-SPSS 26.0 software, using nonparametric statistical tests. The results show a post-exercise TL 5.54% longer than the pre-exercise aTL, although there was no statistically significant difference between the pre- and post- intervention aTL (p=0.750). Likewise, there was no significant difference in the variation of TL between patients with respect to the presence of CVRFs such as comorbidities (p=0.396), elevated lipid profile (0.762), arterial hypertension (p=0.659) or CVD (p=0.81). These results suggest a possible maintenance effect of TL due to the exercise program, independently of the patient's initial cardiovascular status; however, taking into account that this study only contemplated physical activity, the effect observed may be influenced by factors, such as diet, which may act as additional protective factors; for this reason it is not possible to relate physical activity with a telomere maintenance effect in patients with CVD, so it is necessary to conduct a study that includes the monitoring of other possible variables that may influence TL.
Cardiovascular diseases (CVD) are multifactorial disorders that, according to the World Health Organization (WHO), are the leading cause of mortality in Colombia and worldwide. The development of these pathologies is related to various environmental, metabolic and genetic risk factors; among the genetic factors, there are biomarkers with the potential to predict the risk of CVD. One of these biomarkers is telomere length (TL), which are structures at the end of the chromosome that function as a marker of biological aging. This is because over time they reduce in length due to cell division, which generates chromosomal instability and cellular senescence. In addition to cell division, factors such as diseases or lifestyles have been related to changes in TL; among these, physical activity is associated with a protective effect on TL, being also a recommended protocol in patients for the treatment of CVD. However, the cause-effect relationship between physical activity, TL and CVD is unknown. The present study aimed to analyze the effect of an exercise program on telomere length in patients diagnosed with CVD in the city of Barranquilla. The study participants were selected considering the inclusion and exclusion criteria, from a list of patients treated for cardiovascular disease. The selected patients were scheduled for a cardiology evaluation, where the presence of cardiovascular risk factors (CVRF) was recorded, and a venous blood sample was taken to determine the pre-intervention TL. Subsequently, each patient was given the exercise protocol for 3 months, and at the end of the protocol, the participants were summoned to a second blood sampling to determine the post-intervention TL. The samples were processed in triplicate using the real-time quantitative polymerase chain reaction (qPCR) technique. For each sample, a first reaction targeting the telomere and a second reaction targeting the 36B4 gene were performed, which was used as a reference to determine the number of genome copies per reaction for each patient. Additionally, a calibration curve was determined, using serial dilutions of synthesized oligomers of known size of telomere sequence and 36B4 gene, to calculate an absolute TL (aTL). The data obtained were exported and analyzed using Excel and IBM-SPSS 26.0 software, using nonparametric statistical tests. The results show a post-exercise TL 5.54% longer than the pre-exercise aTL, although there was no statistically significant difference between the pre- and post- intervention aTL (p=0.750). Likewise, there was no significant difference in the variation of TL between patients with respect to the presence of CVRFs such as comorbidities (p=0.396), elevated lipid profile (0.762), arterial hypertension (p=0.659) or CVD (p=0.81). These results suggest a possible maintenance effect of TL due to the exercise program, independently of the patient's initial cardiovascular status; however, taking into account that this study only contemplated physical activity, the effect observed may be influenced by factors, such as diet, which may act as additional protective factors; for this reason it is not possible to relate physical activity with a telomere maintenance effect in patients with CVD, so it is necessary to conduct a study that includes the monitoring of other possible variables that may influence TL.
Descripción
Palabras clave
Longitud telomérica, Actividad física, Telómero, Enfermedad cardiovascular, Telomere length, Physical activity, Telomere, Cardiovascular disease
