FIBROMOL: Pathophysiology of the vascular endothelium

Centro de Biología Molecular Severo Ochoa. Consejo Superior de Investigaciones Cientiificas Group Leader and Coordinator: Santiago Lamas.  This email address is being protected from spambots. You need JavaScript enabled to view it.


The main objective of this group is the analysis of the molecular mechanisms involved in the development of cardiovascular diseases. A particularly interesting project deals with the role of ET-1 in the context of cardiovascular pathophysiology, more recently focused on its ability to regulate the biological activity of fibroblasts and myofibroblasts and to induce fibrosis. Another important objective of the group in the last few years has been the study of free radicals and their involvement in vascular physiology. Our group has become a reference in this research area both in Spain and abroad. This line of work on free radicals will focus in the next coming years on the study of the role of oxidative stress in the pathophysiology of fibrotic processes.


Links of interest

Members of the group

  • Santiago Lamas Peláez
  • Fernando Rodríguez Pascual
  • Marta Fierro Fernández
  • M. Estrella Soria López
  • Eva Mª Blanco Ruiz
  • Verónica Miguel Herranz
  • Tamara Rosell García

Most relevant publications 2013-2015

  1. Sánchez-Gómez FJ, Calvo E, Bretón-Romero R, Fierro-Fernández M, Anilkumar N, Shah AM, Schröder K, Brandes RP, Vázquez J, Lamas S. NOX4-dependent Hydrogen peroxide promotes shear stress-induced SHP2 sulfenylation and eNOS activation. Free Radic Biol Med. 2015; 89:419-430.
  2. Fierro-Fernández M, Busnadiego Ó, Sandoval P, Espinosa-Díez C, Blanco-Ruiz E, Rodríguez M, Pian H, Ramos R, López-Cabrera M, García-Bermejo ML, Lamas S. miR-9-5p suppresses pro-fibrogenic transformation of fibroblasts and prevents organ fibrosis by targeting NOX4 and TGFBR2. EMBO Rep. 2015; 16(10):1358-77.
  3. Busnadiego O, Loureiro-Álvarez J, Sandoval P, Lagares D, Dotor J, Pérez-Lozano ML, López-Armada MJ, Lamas S, López-Cabrera M, Rodríguez-Pascual F. A pathogenetic role for endothelin-1 in peritoneal dialysis-associated fibrosis. J Am Soc Nephrol. 2015; 26(1):173-82.
  4. González-Santamaría J, Villalba M, Busnadiego O, López-Olañeta MM, Sandoval P, Snabel J, López-Cabrera M, Erler JT, Hanemaaijer R, Lara-Pezzi E, Rodríguez-Pascual F. Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunction. Cardiovasc Res. 2015. pii: cvv214.
  5. Espinosa-Diez C, Fierro-Fernández M, Sánchez-Gómez F, Rodríguez-Pascual F, Alique M, Ruiz-Ortega M, Beraza N, Martínez-Chantar ML, Fernández-Hernando C, Lamas S. Targeting of Gamma-Glutamyl-Cysteine Ligase by miR-433 Reduces Glutathione Biosynthesis and Promotes TGF-β-Dependent Fibrogenesis. Antioxid Redox Signal. 2014 Oct 29
  6. Rodríguez-Pascual F, Busnadiego O, González-Santamaría J. The profibrotic role of endothelin-1: is the door still open for the treatment of fibrotic diseases? Life Sci. 2014; 118(2):156-64.
  7. Sánchez-Gómez FJ, Espinosa-Díez C, Dubey M, Dikshit M, Lamas S. S-glutathionylation: relevance in diabetes and potential role as a biomarker. Biol Chem. 2013; 394(10):1263-80.
  8. Bretón-Romero R, Kalwa H, Lamas S, Michel T. Role of PTEN in modulation of ADP-dependent signaling pathways in vascular endothelial cells. Biochim Biophys Acta. 2013; 1833(12):2586-95
  9. Olmos Y, Sánchez-Gómez FJ, Wild B, García-Quintans N, Cabezudo S, Lamas S, Monsalve M. SirT1 regulation of antioxidant genes is dependent on the formation of a FoxO3a/PGC-1α complex. Antioxid Redox Signal. 2013; 19(13):1507-21.
  10. Busnadiego O, González-Santamaría J, Lagares D, Guinea-Viniegra J, Pichol-Thievend C, Muller L, Rodríguez-Pascual F. LOXL4 is induced by transforming growth factor β1 through Smad and JunB/Fra2 and contributes to vascular matrix remodeling. Mol Cell Biol. 2013; 33(12):2388-401.

Most relevant publications 2010-2012

  1. Lagares D, Busnadiego O, García-Fernández RA, Kapoor M, Liu S, Carter DE, Abraham D, Shi-Wen X, Carreira P, Fontaine BA, Shea BS, Tager AM, Leask A, Lamas S, Rodríguez-Pascual F. Inhibition of focal adhesion kinase prevents experimental lung fibrosis and myofibroblast formation. Arthritis Rheum. 2012; 64(5):1653-64.
  2. Bretón-Romero R, González de Orduña C, Romero N, Sánchez-Gómez FJ, de Álvaro C, Porras A, Rodríguez-Pascual F, Laranjinha J, Radi R, Lamas S. Critical role of hydrogen peroxide signaling in the sequential activation of p38 MAPK and eNOS in laminar shear stress. Free Radic Biol Med. 2012;52(6):1093-100
  3. Rodríguez P, Higueras MA, González-Rajal A, Alfranca A, Fierro-Fernández M, García-Fernández RA, Ruiz-Hidalgo MJ, Monsalve M, Rodríguez-Pascual F, Redondo JM, de la Pompa JL, Laborda J, Lamas S. The non-canonical NOTCH ligand DLK1 exhibits a novel vascular role as a strong inhibitor of angiogenesis. Cardiovasc Res. 2012; 93(2):232-41.
  4. Redondo-Horcajo M., Romero N., Martínez-Acedo P., Martínez-Ruiz A, Quijano C, Lourenço CF, Movilla N, Enríquez JA, Rodríguez-Pascual F, Rial E, Radi R, Vázquez J, Lamas S. Cyclosporine A-Induced Nitration of Tyrosine 24 MnSOD in Endothelial Cells: Role of Mitochondrial Superoxide. Cardiovascular research 2010 87 (2): 356-65.
  5. Lagares D., García-Fernández R.A., López Jiménez C., Magán-Marchal N., Busnadiego O., Lamas S., Rodríguez-Pascual F. Endothelin-1 contributes to the effect of transforming growth factor-β1 on wound repair and skin fibrosis. Arthritis and Rheumatism, 2010. 62 (3) 878-89.
  6. Holton M.L, Mohamed T.M.A, Oceandy D., Wang W., Lamas S., Emerson M., Neyses L., and Armesilla. AL Endothelial nitric oxide synthase activity is inhibited by the plasma membrane calciumATPase in human endothelial cells Cardiovascular research, 87(3):440-8. 2010.
  7. Borniquel S., García-Quintáns N., Valle I., Olmos Y., Wild B., Martínez-Granero F., Soria E., Lamas S., Monsalve M. Inactivation of Foxo3a and subsequent downregulation of PGC-1 {alpha} mediates nitric oxide induced endothelial cell migration. Mol Cell Biol, 2010 30 (16):4035-44. 2010.
  8. Raoch V., Rodríguez-Pascual F., López-Martínez V., Medrano-Andrés D., Rodríguez-Puyol M., Lamas S., Rodríguez-Puyol D., López-Ongil S. Nitric Oxide Decreases the Expression of Endothelin-Converting Enzyme-1 Through mRNA Destabilization Arterioscler Thromb Vasc Biol. 2011. 31(11): 2577-2585.
  9. Loureiro J., Aguilera A., Selgas R., Sandoval P., Albar-Vizcaíno P., Pérez-Lozano M.L, Ruiz-Carpio V., Majano P.L., Lamas S., Rodríguez-Pascual F., Borras-Cuesta F., Dotor J., López-Cabrera M. Blocking TGF1 protects the peritoneal membrane from dialysate-induced damage. J Am Soc Nephrol. 2011; 22(9):1682-95.
  10. Martínez-Ruiz A., Cadenas S., Lamas S. Nitric Oxide signaling: Classical, less clasical and nonclassical mechanisms. Free Radic Biol Med. 2011 51(1):17-29.


Use of Dlk-1 like angiogenesis inhibitor Nº DE SOLICITUD: P201031547

European Patent Application "Compounds for prevention and/or treatment of fibrotic diseases" Application No/Patent No 14382239.3-1401