Publication: Bases genético-moleculares de la Hipertensión Arterial Pulmonar, su expresión fenotípica en la población española y su papel en las formas poco frecuentes de Hipertensión Arterial Pulmonar
Loading...
Official URL
Full text at PDC
Publication Date
2022-04-19
Authors
Advisors (or tutors)
Editors
Journal Title
Journal ISSN
Volume Title
Publisher
Universidad Complutense de Madrid
Citations
Exportar
Abstract
La Hipertensión Arterial Pulmonar (HAP) es una enfermedad grave y poco frecuente que afecta a las arterias pulmonares de mediano y pequeño calibre, provocando su estrechamiento progresivo. Esto conlleva un aumento de la poscarga en el ventrículo derecho que desencadena Insuficiencia Cardiaca y, si no se corrige, puede llevar a la muerte. En las últimas dos décadas se han producido grandes avances en el conocimiento de las bases genético-moleculares de la HAP, describiéndose una amplia variedad de vías moleculares implicadas. Hasta la fecha, se han relacionado 12 genes con alto nivel de evidencia y 5 genes con menor evidencia. Más aún, las técnicas de secuenciación masiva han permitido la identificación de nuevos genes candidatos. El principal gen relacionado con esta enfermedad codifica la proteína bone morphogenic protein receptor type 2 (BMPR2), un receptor de la super familia transforming growth factor beta (TGF-β). Otros genes implicados en la HAP son: canales de potasio (KCNK3, KCNA5, ABCC8), T-box transcription factor 4 (TBX4), y otros genes de la vía TGF-β/BMP(BMP9/GDF2, SMAD1, SMAD4, SMAD9, BMPR1B). Así mismo, cada vez existe más evidencia de la afectación de otros genes en otras vías patogénicas. Más recientemente, se ha postulado la teoría de “la segunda agresión” debido a la presencia de dos variantes genéticas responsables en una misma persona. Esto hace necesario el uso de técnicas de secuenciación masiva para estudiar un conjunto de genes, todo el exoma e, incluso, todo el genoma...
Pulmonary Arterial Hypertension is a rare and severe condition, characterized by progressive obliteration of small-resistance pulmonary arteries and arterioles. This rise in pulmonary vascular pressure and resistance results in right heart failure and death. In the last two decades, knowledge of hereditary predisposition to PAH has drastically increased. Genes described in PAH are associated with a great variety of molecular pathways. To date, 12 genes have been associated with PAH with a high level of evidence, and 5 have been associated with alow level of evidence. Furthermore, high-throughput sequencing (HTS) technologies have led to the identification of novel associated genes. The main gene involved in PAH encodes the bone morphogenic protein receptor type 2 (BMPR2), a receptor belonging to the transforming growth factor beta (TGF-β) superfamily. Other genes have also been identified: potassium channel genes(KCNK3, KCNA5, ABCC8), T-box transcription factor 4 (TBX4), and other genes in the TGF-β/BMP signaling pathway (BMP9/GDF2, SMAD1, SMAD4, SMAD9, BMPR1B). Also, there is increasing evidence for the involvement of other genes in PAH with less frequency and in different pathways. More recently, a “second hit” hypothesis came up due to the identification of two pathogenic variants in two genes related to PAH. This makes necessary novel approaches using Next Generation Sequencing (NGS) to obtain information from a set of genes, the entire exome or even the whole genome...
Pulmonary Arterial Hypertension is a rare and severe condition, characterized by progressive obliteration of small-resistance pulmonary arteries and arterioles. This rise in pulmonary vascular pressure and resistance results in right heart failure and death. In the last two decades, knowledge of hereditary predisposition to PAH has drastically increased. Genes described in PAH are associated with a great variety of molecular pathways. To date, 12 genes have been associated with PAH with a high level of evidence, and 5 have been associated with alow level of evidence. Furthermore, high-throughput sequencing (HTS) technologies have led to the identification of novel associated genes. The main gene involved in PAH encodes the bone morphogenic protein receptor type 2 (BMPR2), a receptor belonging to the transforming growth factor beta (TGF-β) superfamily. Other genes have also been identified: potassium channel genes(KCNK3, KCNA5, ABCC8), T-box transcription factor 4 (TBX4), and other genes in the TGF-β/BMP signaling pathway (BMP9/GDF2, SMAD1, SMAD4, SMAD9, BMPR1B). Also, there is increasing evidence for the involvement of other genes in PAH with less frequency and in different pathways. More recently, a “second hit” hypothesis came up due to the identification of two pathogenic variants in two genes related to PAH. This makes necessary novel approaches using Next Generation Sequencing (NGS) to obtain information from a set of genes, the entire exome or even the whole genome...
Description
Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 15-12-2021