title: Lamin A is involved in the development of vascular calcification induced by chronic kidney failure and phosphorus load.
abstract: Vascular calcification remains one of the main factors associated to morbidity and mortality in both ageing and chronic kidney disease. Both hyperphosphataemia, a well-known promoter of vascular calcification, and abnormal processing defects of lamin A/C have been associated to ageing. The main aim of this study was to analyse the effect of phosphorus load in the differential expression pattern of genes and proteins, particularly of lamin A/C, which are involved in phenotypic change of the vascular smooth muscle cells to osteoblast-like cells. The in vivo study of the calcified abdominal aortas from nephrectomized rats receiving a high phosphorus diet showed among others, a repression of muscle related proteins and overexpression of lamin A/C. Similar results were observed in vitro, where primary vascular smooth muscle cells cultured in calcifying medium showed increased expression of prelamin A and lamin A and abnormalities in the nuclear morphology. Co-immunoprecipitation assays showed novel and important physical interactions between lamin A and RUNX2 during the process of calcification. In fact, the knockdown of prelamin A and lamin A inhibited the increase of Runx2, osteocalcin and osteopontin gene expression, calcium deposition, nuclear abnormalities and the RUNX2 protein translocation into the nucleus of the cell. These in vivo and in vitro results highlight the important role played by lamin A in the process of vascular calcification.
authors.affiliation: Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, REDinREN del ISCIII, Hospital Universitario Central de Asturias, University of Oviedo, 33006 Oviedo, Asturias, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Quirós-González
authors.affiliation: Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, REDinREN del ISCIII, Hospital Universitario Central de Asturias, University of Oviedo, 33006 Oviedo, Asturias, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Román-García
authors.affiliation: Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, REDinREN del ISCIII, Hospital Universitario Central de Asturias, University of Oviedo, 33006 Oviedo, Asturias, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Alonso-Montes
authors.affiliation: Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, REDinREN del ISCIII, Hospital Universitario Central de Asturias, University of Oviedo, 33006 Oviedo, Asturias, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Barrio-Vázquez
authors.affiliation: Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, REDinREN del ISCIII, Hospital Universitario Central de Asturias, University of Oviedo, 33006 Oviedo, Asturias, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Carrillo-López
authors.affiliation: Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, REDinREN del ISCIII, Hospital Universitario Central de Asturias, University of Oviedo, 33006 Oviedo, Asturias, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Naves-Díaz
authors.affiliation: Division of Hepatology and Gene Therapy, Proteomics, Genomics and Bioinformatics Unit, Centre for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Mora
authors.affiliation: Division of Hepatology and Gene Therapy, Proteomics, Genomics and Bioinformatics Unit, Centre for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain.
authors.forename: Fernando José
authors.initials: FJ
authors.lastname: Corrales
authors.affiliation: Department of Renal Physiology, REDinREN del ISCIII, Faculty of Biology, University of Salamanca, 37007 Salamanca, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: López-Hernández
authors.affiliation: Department of Systems Biology, REDinREN del ISCIII, Faculty of Medicine, University of Alcalá, Alcalá de Henares, 28801, Madrid, Spain.
authors.forename: María Piedad
authors.initials: MP
authors.lastname: Ruiz-Torres
authors.affiliation: Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, REDinREN del ISCIII, Hospital Universitario Central de Asturias, University of Oviedo, 33006 Oviedo, Asturias, Spain. Electronic address: cannata@hca.es.
authors.forename: Jorge Benito
authors.initials: JB
authors.lastname: Cannata-Andía
authors.affiliation: Bone and Mineral Research Unit, Instituto Reina Sofía de Investigación, REDinREN del ISCIII, Hospital Universitario Central de Asturias, University of Oviedo, 33006 Oviedo, Asturias, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Fernández-Martín
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D004032:Diet; D055785:Gene Knockdown Techniques; D047468:Immunoprecipitation; D007676:Kidney Failure, Chronic / Q000150:complications*; D034904:Lamin Type A / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D010758:Phosphorus / Q000009:adverse effects*; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry; D061205:Vascular Calcification / Q000097:blood / Q000209:etiology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D050659:Core Binding Factor Alpha 1 Subunit; D034904:Lamin Type A; C090764:prelamin A; D010758:Phosphorus
keywords: Ageing; Animal models; Chronic kidney disease; Lamin a; Phosphorus load; Proteomics; Runx2; Vascular calcification