INTESTINAL MICROBIOTA, NEW DIANA IN THE TREATMENT OF CARDIOVASCULAR COMPLICATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS (Q3136071)
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Project Q3136071 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | INTESTINAL MICROBIOTA, NEW DIANA IN THE TREATMENT OF CARDIOVASCULAR COMPLICATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS |
Project Q3136071 in Spain |
Statements
96,800.0 Euro
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121,000.0 Euro
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80.0 percent
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1 January 2018
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31 December 2020
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UNIVERSIDAD DE GRANADA
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37°10'24.60"N, 3°35'58.31"W
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18087
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EL LUPUS ERITEMATOSO SISTEMICO (LES) ES UNA ENFERMEDAD AUTOINMUNE CRONICA QUE AFECTA PROMINENTEMENTE A LOS RIÑONES, AUNQUE TAMBIEN A OTROS ORGANOS COMO LA PIEL O EL SISTEMA NERVIOSO CENTRAL. LA PRINCIPAL CAUSA DE MORTALIDAD EN LES SON LAS ENFERMEDADES CARDIOVASCULARES. LA HIPERTENSION ES EL PRINCIPAL FACTOR DE RIESGO PARA LA PROGRESION DE ENFERMEDAD RENAL, VASCULAR Y CARDIACA, Y EN SU EVOLUCION PARTICIPA EL SISTEMA INMUNOLOGICO. SE HA DESCRITO LA EXISTENCIA DE DISBIOSIS INTESTINAL EN ANIMALES Y EN PACIENTES CON LES. ESTA ALTERACION DE LA MICROBIOTA PROVOCA LA MODIFICACION DE LA RESPUESTA INMUNOLOGICA (P.E. AUMENTO DE CELULAS TH17 Y REDUCCION DE TREG) Y LA LIBERACION DE METABOLITOS (ACIDO GRASOS DE CADENA CORTA, SCFAS Y OXIDO DE TRIMETILAMINA, TMAO) QUE PODRIAN INCIDIR EN LA PARED VASCULAR ORIGINANDO INFLAMACION, INCREMENTO DE LA PRODUCCION DE ESPECIES REACTIVAS DE OXIGENO, REDUCCION DE LA BIODISPONIBILIDAD DEL OXIDO NITRICO Y DE LA RELAJACION DEPENDIENTE DE ENDOTELIO, FACILITANDO EL ESTABLECIMIENTO DE HIPERTENSION. POR OTRO LADO, LA MODIFICACION DE LA MICROBIOTA MEDIANTE EL CONSUMO DE DETERMINADAS BACTERIAS PROBIOTICAS O DE SUSTANCIAS PREBIOTICAS PODRIA EJERCER ACCIONES INMUNOMODULADORAS, INCREMENTANDO LA ACUMULACION DE LINFOCITOS TREG EN LA VASCULATURA Y/O REDUCIENDO LOS TH17, CON LA CONSIGUIENTE DISMINUCION DE SU ESTADO PROINFLAMATORIO Y PROOXIDANTE Y REDUCIENDO LA PRESION ARTERIAL. ADICIONALMENTE, EL CONSUMO DE SCFAS O LA INHIBICION FARMACOLOGICA DE ENZIMAS BACTERIANAS IMPLICADAS EN LA PRODUCCION DE TMAO PODRIA EJERCER UN EFECTO PROTECTOR CARDIOVASCULAR. LOS OBJETIVOS DE ESTE PROYECTO SON: A) ANALIZAR EL PAPEL DE LA FLORA INTESTINAL EN EL DESARROLLO Y MANTENIMIENTO DEL LES EN UN MODELO GENETICO (RATON HEMBRA NZBWF1) Y OTRO INDUCIDO MEDIANTE ACTIVACION TLR-7 CON IMIQUIMOD, CENTRANDONOS EN LA RELACION ENTRE SISTEMA INMUNOLOGICO Y FUNCION ENDOTELIAL; B) ANALIZAR LA PARTICIPACION DE LA VIA SCFAS-RECEPTORES OLFATORIOS EN LA COMPLICACIONES CARDIOVASCULARES DE ESTOS DOS MODELOS DE LES; C) ANALIZAR LA PARTICIPACION DE TMAO EN LA COMPLICACIONES CARDIOVASCULARES DEL MODELO GENETICO DE LES, Y D) ESTABLECER EL POSIBLE PAPEL PROTECTOR DE LA SUPLEMENTACION DIETETICA CON DETERMINADOS PROBIOTICOS Y PREBIOTICOS SOBRE EL DESARROLLO DE HIPERTENSION EN LES Y SU RELACION CON EL BALANCE ENTRE LINFOCITOS TH17 Y TREG. (Spanish)
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SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) IS A CHRONIC AUTOIMMUNE DISEASE THAT AFFECT PROMINENTLY THE KIDNEY, AND OTHER ORGANS SUCH AS THE SKIN AND THE CENTRAL NERVOUS SYSTEM. THE MAIN CAUSE OF MORTALITY IN SLE IS CARDIOVASCULAR DISEASE. HYPERTENSION IS THE MAIN RISK FACTOR IN RENAL, VASCULAR AND HEART DISEASE PROGRESSION, AND THE IMMUNE SYSTEM PLAYS A ROLE IN ITS DEVELOPMENT. THE PRESENCE OF DYSBIOSIS IN SLE PATIENTS AND ANIMALS HAS BEEN DESCRIBED. THIS ALTERATION OF THE MICROBIOTA TRIGGERS THE MODIFICATION OF THE IMMUNE RESPONSE (E.G. INCREASE IN TH17 CELLS AND DECREASE IN TREG) AND THE RELEASE OF METABOLITES (SHORT CHAIN FATTY ACIDS, SCFAS AND TRIMETHYLAMINE N-OXIDE, TMAO) CAPABLE OF ALTERING THE VASCULAR WALL CAUSING INFLAMMATION, AN INCREASE IN REACTIVE OXYGEN SPECIES, AND A DECREASE IN NITRIC OXIDE BIOAVAILABILITY AND ENDOTHELIUM-DEPENDENT RELAXATION, FACILITATING THE ESTABLISHMENT OF HYPERTENSION. ON THE OTHER HAND, THE MODIFICATION OF THE MICROBIOTA THROUGH THE CONSUMPTION OF CERTAIN PROBIOTIC BACTERIA OR PREBIOTIC SUBSTANCES COULD EXERT IMMUNOMODULATORY ACTIONS, BOOSTING THE ACCUMULATION OF TREG LYMPHOCYTES IN THE VASCULATURE AND/OR REDUCING TH17, WITH THE CONSEQUENT DECLINE IN ITS PRO-INFLAMMATORY AND PRO-OXIDANT STATE, AND LOWERING ARTERIAL BLOOD PRESSURE. ADDITIONALLY, SCFAS CONSUMPTION OR THE PHARMACOLOGICAL INHIBITION OF BACTERIAL ENZYMES INVOLVED IN THE PRODUCTION OF TMAO COULD DEPLOY A CARDIOVASCULAR PROTECTIVE EFFECT. THE OBJECTIVES OF THIS PROJECT ARE: A) TO ANALYZE THE ROLE OF INTESTINAL FLORA IN THE DEVELOPMENT AND MAINTENANCE OF SLE IN A GENETIC MODEL (NZBWF1 FEMALE MOUSE) AND AN IMIQUIMOD-INDUCED TLR ACTIVATION MODEL, FOCUSING IN THE LINK BETWEEN IMMUNE SYSTEM AND ENDOTHELIAL FUNCTION; B) TO ANALYZE THE PARTICIPATION OF THE SCFAS-OLFATORY RECEPTORS PATHWAY IN THE CARDIOVASCULAR COMPLICATIONS IN THOSE SLE MODELS; C) TO ANALYZE THE PARTICIPATION OF TMAO IN CARDIOVASCULAR COMPLICATIONS IN THE GENETIC MODEL OF SLE, AND D) TO ESTABLISH THE POSSIBLE PROTECTIVE ROLE OF DIETETIC SUPPLEMENTATION WITH CERTAIN PROBIOTICS AND PREBIOTICS ON THE DEVELOPMENT OF HYPERTENSION IN SLE AND ITS LINK TO THE BALANCE BETWEEN TH17 AND TREG LYMPHOCYTES (English)
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Granada
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Identifiers
SAF2017-84894-R
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