Research groups

GE06 Pathophysiology of renal and vascular damage

The group GE-06 “Pathophysiology of renal and vascular damage” is an Emerging Group of the IMIBIC. Our group is composed of clinical and basic researches working together to improve the knowledge of these pathologies and to translate the basic research into the clinical practice. We integrate into our studies experts in specific areas such as Immunology, Pathology, Pharmacology, Cardiology, and Nephrology to carry out several multidisciplinary research projects. The group is led by Juan Antonio Moreno, a Ramón y Cajal tenure track researcher associated with the Department of Cell Biology, Physiology and Immunology (University of Cordoba) since 2019 (103 articles published, cumulative IF: 340; H-index: 30).

Renal and cardiovascular diseases constitute major health problems, with elevated mortality and morbidity rates. Our group is unraveling novel pathogenic mechanisms involved in the development of these diseases. Our primary goal is to understand the basis for alterations in renal and vascular wall to identify new molecules involved in the progression of these pathologies that may be used as potential diagnostic/prognosis biomarkers and to develop novel therapeutic approaches and their eventual clinical translation. Specifically, we are interested in certain cellular and molecular aspects (oxidation, inflammation, apoptosis, fibrosis, transcription factors, intracellular signaling, cytokines, etc.) involved in the progression of a number of pathologies (atherothrombosis, diabetic nephropathy, glomerular diseases, acute renal injury, nephrotoxicity, renal fibrosis, among others). To achieve these objectives, our group has applied a varied set of cellular and molecular biology techniques (flow cytometry, confocal microscopy, activity assays, gene/protein expression analysis, etc) in suitable cultured cells, experimental animal models and human samples.

We have recently observed that one of the mechanisms involved in the loss of renal function is the massive accumulation of hemoglobin (Hb), myoglobin, and other heme-related proteins. Massive accumulation of hemoprotein in the kidney promotes acute kidney injury and chronic kidney disease, as observed in patients suffering from glomerular macroscopic hematuria and massive/recurrent intravascular hemolysis (atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria and sickle cell disease). A similar pathogenic role of hemoproteins has been demonstrated during the progression of hemorrhagic atherosclerotic plaques. Our group discovered new cellular targets for the adverse effects of hemoproteins (hemoglobin (Hb), myoglobin, and other heme-related proteins) in the kidney and the atherosclerotic plaque. Thus, we identified hemoproteins-mediated injury in macrophages, tubular cells, and podocytes.

We actively collaborate with numerous researchers working in national and international centers (Fundacion Jimenez Diaz, Autonoma University Madrid, Complutense University Madrid, Odense University Hospital, Denmark, Karolinska Institute, Sweden, Paris Diderot School of Medicine, France and University of Debrecen, Hungary, among others). In addition, we are an active member of the National Network on Cardiovascular Diseases (CIBERCV), Spanish Society of Atherosclerosis, Spanish Society of Nephrology (GLOSEN), and the Immunonephrology Working Group of the European Renal Association.

In the last years, we have obtained competitive research projects supported by the National Institute of Health Carlos III (ISCIII), Spanish Society of Atherosclerosis, Spanish Society of Nephrology, Iñigo Alvarez de Toledo Renal Foundation, and the IMIBIC-Roche grant, as well as different projects funded by international biotechnological companies.

Research Lines

Networks

    CIBERCV - CIBER on Cardiovascular Diseases

    ERA-EDTA - Immunonephrology Working Group. European Renal Association – European Dialysis and Transplant Association

    GLOSEN - Spanish group for glomerulonephritis

    VascAgeNet  - COST Action CA18216. 2019-2023. - Network for Research in Vascular Ageing. European Cooperation in Science and Technology. Horizon 2020 Framework Programme of the European Union.

Keywords

  • kidney
  • hemoglobin
  • myoglobin
  • cell death
  • oxidative stress
  • acute kidney injury
  • intravascular Hemolysis
  • rhabdomyolysis
  • Nrf2
  • macrophages
  • podocytes
  • IgA nephropathy

Additional Information

Training capacity of the group

Supervised thesis in the last 5 years:

Renal damage induced by glomerular hematuria. 2016. Complutense University. Madrid.

Novel pathophysiological mechanisms involved in renal and vascular damage associated to hemoproteins accumulation. 2016. Autonoma University. Madrid.

Molecular mechanisms involved in acute kidney injury associated to rhabdomyolysis. 2018.

Value of hematuria as a risk factor in IgA Nephropathy. Complutense University. Madrid. 2020.

Human resources obtained in national or international calls in the last 5 years:

Conchita Rábago Fellowship, Fundación Conchita Rábago, 2016-2018.

FPU16/03600. MICINN, 2017-2021

PFIS FI18/00310. Instituto de Salud Carlos III, 2019-2022

Cordoba University PhD Fellowship, 2020-2022

Sara Borrell CD17/00030. Instituto de Salud Carlos III, 2018-2019

Sara Borrell CD19/00021. Instituto de Salud Carlos III, 2020-2022

Participation in international R&D&I projects in the last 5 years:

Effect of Budesonide Treatment on Hb-associated renal biomarkers in patients with IgA nephropathy. Pharmalink AB, Sweden. 2017-2020.

COST Action CA18216 - Network for Research in Vascular Ageing. European Cooperation in Science and Technology. Horizon 2020 Framework Programme of the European Union. 2019-2023.

FP7-HEALTH-2013.4.1-4-602422. KidneyConnect: European Kidney-Podocyte Research Platform. 2013-2016.

Immnunonephrology working group (IWG). The European Renal Association – European Dialysis and Transplant Association (ERA-EDTA). 2018-2020

Future Challenges:

To identify new pathological effects and novel molecular pathways involved in vascular and renal damage.

To validate the effectiveness of novel therapeutic strategies in these pathological conditions.

To analyze the prognostic value of different biomarkers differently expressed in biopsies, blood, and urine samples from patients with renal and vascular diseases.

Projects

PROJECTS IN 2020

Ongoing projects

National

Juan Antonio Moreno Gutiérrez; Estudio de nuevos mecanismos y dianas terapéuticas implicadas en el daño renal agudo y crónico en patologías asociadas a acumulación renal de hemoglobina; Funding Agency: INSTITUTO DE SALUD CARLOS III; Reference: PI17/00130

PROJECTS IN 2019

Ongoing projects

National

Juan Antonio Moreno Gutiérrez; Estudio de nuevos mecanismos y dianas terapéuticas implicadas en el daño renal agudo y crónico en patologías asociadas a acumulación renal de hemoglobina; Funding Agency: National Instituteof Health Carlos III (ISCIII); Reference: PI17/00130

Juan Antonio Moreno Gutiérrez; Desarrollo de nuevos inductores de Nrf2 multidiana para el tratamiento de la enfermedad renal.  PROYECTO IMIBIC-ROCHE 2019.

Juan Antonio Moreno Gutiérrez; Ensayo clínico Fase I-II multicéntrico para evaluar seguridad y eficacia de un medicamento de terapia avanzada basado en una córnea artificial de péptidos similares al colágeno con células epiteliales para el tratamiento de enfermedades corneales severas FIBICO. PI: Miguel González Andrades. (Instituto Maimónides de Investigación Biomédica de Córdoba). 01/01/2020-31/12/2022.

Juan Antonio Moreno Gutiérrez; (team member). RTC-2017-6089-1, Desarrollo de nefrosmil- nueva formulación de liberación prolongada para el tratamiento de nefropatia diabética. RETOS COLABORACION. PI: Jesús Egido de los Rios. (Fundación Jiménez Díaz). 01/01/2018- 31/12/2020.

Juan Antonio Moreno Gutiérrez (team member). Vías patogénicas del daño podocitario inducido por hematuria en la nefropatía IgA. Perspectivas terapéuticas. Fundación Biomédica, Instituto de Investigación Hospital 12 de Octubre. PI: Manuel Praga Terente. (Hospital Universitario 12 de Octubre). 01/01/2019-31/01/2020.

Publications

Publications in 2020

Faroux L, Chen S, Muntane-Carol G, Regueiro A, Philippon F, Sondergaard L, Jorgensen TH, Lopez-Aguilera J, Kodali S, Leon M, Nazif T, Rodes-Cabau J. Clinical impact of conduction disturbances in transcatheter aortic valve replacement recipients: a systematic review and meta-analysis. EUROPEAN HEART JOURNAL. 2020. 41 (29):2771-+ DOI: 10.1093/eurheartj/ehz924 
IF: 22,673 Q: 1 D: 1

Gonzalez-Gonzalez AI, Perestelo-Perez L, Koatz D, Ballester M, Pacheco-Huergo V, Ramos-Garcia V, Torres-Castano A, Rivero-Santana A, Toledo-Chavarri A, Valcarcel-Nazco C, Mateos-Rodilla J, Obaya-Rebollar JC, Garcia-Garcia J, Diaz-Sanchez S, Morales-Cobos . Effectiveness and cost-effectiveness of a virtual community of practice to improve the empowerment of patients with ischaemic heart disease: study protocol of a randomised controlled trial. BMJ OPEN. 2020. 10 (10):- DOI: 10.1136/bmjopen-2020-037374 
IF: 2,496 Q: 2

Martin-Sanchez D, Fontecha-Barriuso M, Martinez-Moreno JM, Ramos AM, Sanchez-Nino MD, Guerrero-Hue M, Moreno JA, Ortiz A, Sanz AB. Ferroptosis and kidney disease. NEFROLOGIA. 2020. 40 (4):384-394 DOI: 10.1016/j.nefro.2020.03.005 
IF: 1,544 Q: 4

Rodrigues-Diez RR, Tejera-Munoz A, Marquez-Exposito L, Rayego-Mateos S, Sanchez LS, Marchant V, Santamaria LT, Ramos AM, Ortiz A, Egido J, Ruiz-Ortega M. Statins: Could an old friend help in the fight against COVID-19?. BRITISH JOURNAL OF PHARMACOLOGY. . 177 (21):4873-4886 DOI: 10.1111/bph.15166 
IF: 7,73 Q: 1 D: 1

Ojeda S, Hidalgo F, Romero M, Mazuelos F, de Lezo JS, Martin E, Lostalo A, Luque A, Gonzalez R, Fernandez A, Lopez-Aguilera J, Segura J, Guerrero N, Pan M. Impact of the repositionable Evolut R CoreValve system on the need for a permanent pacemaker after transcatheter aortic valve implantation in patients with severe aortic stenosis. CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS. 2020. 95 (4):783-790 DOI: 10.1002/ccd.28327 
IF: 2,044 Q: 3

Caro-Ordieres T, Marin-Royo G, Opazo-Rios L, Jimenez-Castilla L, Moreno JA, Gomez-Guerrero C, Egido J. The Coming Age of Flavonoids in the Treatment of Diabetic Complications. JOURNAL OF CLINICAL MEDICINE. 2020. 9 (2):- DOI: 10.3390/jcm9020346 
IF: 3,303 Q: 1

Esteras R, Fox JG, Geddes CC, Mackinnon B, Ortiz A, Moreno JA. Hematuria Is Associated with More Severe Acute Tubulointerstitial Nephritis. JOURNAL OF CLINICAL MEDICINE. 2020. 9 (7):- DOI: 10.3390/jcm9072135 
IF: 3,303 Q: 1

Carmona A, Guerrero F, Jimenez MJ, Ariza F, Aguera ML, Obrero T, Noci V, Munoz-Castaneda JR, Rodriguez M, Soriano S, Moreno JA, Martin-Malo A, Aljama P. Inflammation, Senescence and MicroRNAs in Chronic Kidney Disease. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY. 2020. 8 ():- DOI: 10.3389/fcell.2020.00739 
IF: 5,201 Q: 1

Opazo-Rios L, Mas S, Marin-Royo G, Mezzano S, Gomez-Guerrero C, Moreno JA, Egido J. Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2020. 21 (7):- DOI: 10.3390/ijms21072632 
IF: 4,556 Q: 1

Rayego-Mateos S, Morgado-Pascual JL, Opazo-Rios L, Guerrero-Hue M, Garcia-Caballero C, Vazquez-Carballo C, Mas S, Sanz AB, Herencia C, Mezzano S, Gomez-Guerrero C, Moreno JA, Egido J. Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2020. 21 (11):- DOI: 10.3390/ijms21113798 
IF: 4,556 Q: 1

Guerrero F, Carmona A, Obrero T, Jimenez MJ, Soriano S, Moreno JA, Martin-Malo A, Aljama P. Role of endothelial microvesicles released by p-cresol on endothelial dysfunction. SCIENTIFIC REPORTS. 2020. 10 (1):- DOI: 10.1038/s41598-020-67574-6 
IF: 3,998 Q: 1

Ortiz MR, Diego SR, Ortega MD, Fernandez JJS, Salas RO, Montoro LC, Avalos FC, Aguilera JL, Granados AL, del Prado JMA, Penas ER, Hurtado NP, Fernandez JO, Pan M, Rubio DM. Tissue Doppler velocities for ruling out rejection in heart transplant recipients in the context of myocardial strain imaging: a multivariate, prospective, single-center study. INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING. 2020. 36 (8):1455-1464 DOI: 10.1007/s10554-020-01843-3 
IF: 1,969 Q: 3

Publications in 2019

Guerrero-Hue M, Garcia-Caballero C, Palomino-Antolin A, Rubio-Navarro A, Vazquez-Carballo C, Herencia C, Martin-Sanchez D, Farre-Alins V, Egea J, Cannata P, Praga M, Ortiz A, Egido J, Sanz AB, Moreno JA; Curcumin reduces renal damage associated with rhabdomyolysis by decreasing ferroptosis-mediated cell death. FASEB JOURNAL. 2019 Aug;33(8):8961-8975. doi: 10.1096/fj.201900077R.
IF: 5,595 D: 1

Rubio-Navarro A, Vazquez-Carballo C, Guerrero-Hue M, Garcia-Caballero C, Herencia C, Gutierrez E, Yuste C, Sevillano A, Praga M, Egea J, Cannata P, Cortegano I, de Andres B, Gaspar ML, Cadenas S, Michalska P, Leon R, Ortiz A, Egido J, Moreno JA; Nrf2 Plays a Protective Role Against Intravascular Hemolysis-Mediated Acute Kidney Injury. FRONTIERS IN PHARMACOLOGY. 2019 Jul 3;10:740. doi: 10.3389/fphar.2019.00740
IF: 3,845 Q: 1

Moreno JA, Sevillano A, Gutierrez E, Guerrero-Hue M, Vazquez-Carballo C, Yuste C, Herencia C, Garcia-Caballero C, Praga M, Egido J; Glomerular Hematuria: Cause or Consequence of Renal Inflammation?. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2019 May 5;20(9):2205. doi: 10.3390/ijms20092205.
IF: 3,687 Q: 2

Cavero T, Arjona E, Soto K, Caravaca-Fontán F, Rabasco C, Bravo L, de la Cerda F, Martín N, Blasco M, Ávila A, Huerta A, Cabello V, Jarque A, Alcázar C, Fulladosa X, Carbayo J, Anaya S, Cobelo C, Ramos N, Iglesias E, Baltar J, Martínez-Gallardo R, Pérez L, Morales E, González R, Macía M, Draibe J, Pallardó L, Quintana LF, Espinosa M, Barros X, Pereira F, Cao M, Moreno JA, Rodríguez de Córdoba S, Praga M; Spanish Group for the Study of Glomerular Diseases (GLOSEN). 2019. Severe and malignant hypertension are common in primary atypical hemolytic uremic syndrome. Kidney international. 2019 Oct;96(4):995-1004. doi: 10.1016/j.kint.2019.05.014.

Sevillano AM, Diaz M, Caravaca-Fontán F, Barrios C, Bernis C, Cabrera J, Calviño J, Castillo L, Cobelo C, Delgado-Mallén P, Espinosa M, Fernandez-Juarez G, Fernandez-Reyes MJ, Garcia-Osuna R, Garcia P, Goicoechea M, Gonzalez-Cabrera F, Guzmán DA, Heras M, Martín-Reyes G, Martinez A, Olea T, Peña JK, Quintana LF, Rabasco C, López Revuelta K, Rodas L, Rodriguez-Mendiola N, Rodriguez E, San Miguel L, Sanchez de la Nieta MD, Shabaka A, Sierra M, Valera A, Velo M, Verde E, Ballarin J, Noboa O, Moreno JA, Gutiérrez E, Praga M; Spanish Group for the Study of Glomerular Diseases (GLOSEN). 2019. IgA Nephropathy in Elderly Patients.Clinical journal of the American Society of Nephrology: CJASN. 2019 Aug 7;14(8):1183-1192. doi: 10.2215/CJN.13251118.

Clinical Research

Active in 2019

Estudio observacional y retrospectivo de las características clínicas y patológicas del carcinoma de células de Merkel (CCM) entre 2012 y 2016 en España. Estudio MECCAS.
PI: Dr. Alicia Sanz Zorrilla

Members

Principal Investigator
Juan Antonio Moreno Gutiérrez

Researchers
Francisco Javier Mendoza García
Rafael Alejandro Pérez Écija

Post-Doctoral Researchers
María del Carmen Durán Torralba
José López Aguilera
José Luis Morgado Pascual
Sandra Rayego Mateos
Ana María Rodríguez Almodóvar

Pre-Doctoral Researchers
Cristina García Caballero
Melania Guerrero Hue
Alicia Sanz Zorrilla

Nursing, Technical, and Administrative Staff
Mercedes Vallejo Mudarra