| Autor: |
Lorente-Herraiz L; Departamento de Biomedicina Molecular, Centro de Investigaciones Biológicas Margaritas Salas, 28040 Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain., Cuesta AM; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain.; Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.; Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain., Granado J; Departamento de Biomedicina Molecular, Centro de Investigaciones Biológicas Margaritas Salas, 28040 Madrid, Spain., Recio-Poveda L; Departamento de Biomedicina Molecular, Centro de Investigaciones Biológicas Margaritas Salas, 28040 Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain., Botella LM; Departamento de Biomedicina Molecular, Centro de Investigaciones Biológicas Margaritas Salas, 28040 Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain., Albiñana V; Departamento de Biomedicina Molecular, Centro de Investigaciones Biológicas Margaritas Salas, 28040 Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain. |
| Abstrakt: |
Cerebral cavernous malformation (CCM) or familial cavernomatosis is a rare, autosomal dominant, inherited disease characterized by the presence of vascular malformations consisting of blood vessels with an abnormal structure in the form of clusters. Based on the altered gene ( CCM1/Krit1 , CCM2 , CCM3 ) and its origin (spontaneous or familial), different types of this disease can be found. In this work we have isolated and cultivated primary endothelial cells (ECs) from peripheral blood of a type 1 CCM patient. Differential functional and gene expression profiles of these cells were analyzed and compared to primary ECs from a healthy donor. The mutation of the familial index case consisted of a heterozygous point mutation in the position +1 splicing consensus between exons 15 and 16, causing failure in RNA processing and in the final protein. Furthermore, gene expression analysis by quantitative PCR revealed a decreased expression of genes involved in intercellular junction formation, angiogenesis, and vascular homeostasis. Cell biology analysis showed that CCM1 ECs were impaired in angiogenesis and cell migration. Taken together, the results obtained suggest that the alterations found in CCM1 ECs are already present in the heterozygous condition, suffering from vascular impairment and somewhat predisposed to vascular damage. |
