MARIA LUISA GUARINO

Dottoressa di ricerca

ciclo: XXXIII



Titolo della tesi: MRP4 OVER-EXPRESSION ROLE ON PLATELET HYPER-REACTIVITY : PROPOSAL FOR A NEW BIOMARKER TO EVALUATE CARDIOVASCULR RISK

The impact of inhibition of multidrug resistance protein 4 (MRP4) on nitric oxide (NO) resistance and on ADP-induced platelet aggregation is unknown. The aim of this investigation was to verify whether platelet NO resistance correlates with MRP4 expression and evaluate whether this can be reduced by in vitro MRP4 inhibition mediated by cilostazol. Moreover, we assessed if inhibition of MRP4-mediated transport reduces ADP-induced platelet reactivity. The inhibitory effect of sodium nitroprusside (SNP), a NO-donor that enhances cyclic guanosine monophosphate (cGMP) cytosolic concentration, was assessed in platelets obtained from aspirin treated patients and in a control population. The inhibitory effect of SNP was evaluated by ADP-induced aggregation in SNP-treated platelets. The impact of MRP4 on ADP-induced platelet aggregation was performed in high on aspirin residual platelet reactivity (HARPR) patients and compared to healthy volunteers (HV), and a control cohort (CTR). In aspirin-treated patients with high levels of MRP4, reduced SNP inhibition was found compared to those with low levels of MRP4. MRP4 inhibition by cilostazol significantly reduced ADP-induced platelet aggregation in HARPR population, and to a lesser extent in HV and CTR populations. In conclusion, cilostazol can mitigate the hyper-reactive platelet phenotype of HARPR patients by reducing residual ADP-induced platelet aggregation and increasing NO-dependent endothelial antiplatelet effects. The precision medicine has an important role to cardiovascular disease prevention and treatment, this approach considers individual’s genetics, lifestyle, phenotypes. In many works it has been shown that platelet hyper reactivity correlates with the over expression of MRP4 and has been evaluated by studying the MRP4 mRNA, our goal instead is to be able to directly dose the protein by using an ELISA kit.

Produzione scientifica

  • 11573/1078271 - 2018 - Impact of Multidrug Resistance Protein-4 Inhibitors on Modulating Platelet Function and High on-Aspirin Treatment Platelet Reactivity (01a Articolo in rivista)
    ALEMANNO, LAURA; MASSIMI, ISABELLA; GUARINO, MARIA LUISA; FRATI, LUIGI; PULCINELLI, FABIO MARIA
  • 11573/1100816 - 2018 - MiR-21 role in aspirin-dependent PPARα and MRP4 up-regulation (01a Articolo in rivista)
    MASSIMI, ISABELLA; ALEMANNO, LAURA; GUARINO, MARIA LUISA; FRATI, LUIGI; PULCINELLI, FABIO MARIA
  • 11573/689461 - 2015 - Arachidonic acid-stimulated platelet tests: Identification of patients less sensitive to aspirin treatment (01a Articolo in rivista)
    TEMPERILLI, FLAVIA; MASSIMI, ISABELLA; GUARINO, MARIA LUISA; ZICARI, ALESSANDRA; PULCINELLI, FABIO MARIA
  • 11573/1230556 - 2018 - Non-steroidal anti-inflammatory drugs increase MRP4 expression in an endometriotic epithelial cell line in a PPARa dependent manner (01a Articolo in rivista)
    MASSIMI, ISABELLA; PULCINELLI, FRANCESCA MARIA; PISCITELLI, VALERIO PIACENTINO; GUARINO, MARIA LUISA; MARCI, ROBERTO; FRATI, LUIGI; MALLOZZI, MADDALENA; FREGA, ANTONIO; CASERTA, DONATELLA
  • 11573/1238243 - 2019 - Aspirin-dependent effects on purinergic P2Y1 receptor express (01a Articolo in rivista)
    MASSIMI, ISABELLA; ALEMANNO, LAURA; GUARINO, MARIA LUISA; MANCONE, MASSIMO; CECCACCI, ANDREA; FRATI, LUIGI; PULCINELLI, FABIO MARIA
  • 11573/787521 - 2015 - Nonsteroidal anti-inflammatory drugs in-vitro and in-vivo treatment and Multidrug Resistance Protein 4 expression in human platelets (01a Articolo in rivista)
    TEMPERILLI, FLAVIA; DI FRANCO, MANUELA; MASSIMI, ISABELLA; GUARINO, MARIA LUISA; GUZZO, MARIA PAOLA; FRATI, LUIGI; PULCINELLI, FABIO MARIA; VALESINI, GUIDO
  • 11573/1281896 - 2020 - Platelet activation and multidrug resistance protein-4 expression in children and adolescents with different subtypes of primary thrombocythemia (01f Lettera, Nota)
    GIONA, FIORINA; MASSIMI, ISABELLA; GUARINO, MARIA LUISA; SANTOPIETRO, MICHELINA; LAURINO, MARICA; TEMPERILLI, FLAVIA; PALUMBO, GIOVANNA; FOA, ROBERTO; PULCINELLI, FABIO MARIA
  • 11573/956293 - 2017 - New platelet functional method for identification of pathogenic antibodies in HIT patients (01a Articolo in rivista)
    GUARINO, MARIA LUISA; MASSIMI, ISABELLA; MARDENTE, STEFANIA; PULCINELLI, FABIO MARIA
  • 11573/1522021 - 2019 - Medicina di laboratorio - La diagnosi di malattia nel laboratorio clinico: collaborazione traduzione (02e Traduzione in volume)
    PULCINELLI, FABIO MARIA; GUARINO, MARIA LUISA; PULCINELLI, FRANCESCA MARIA
  • 11573/1284892 - 2014 - MRP4 Expression and Platelet Activation in Children and Adolescents with Different Subtypes of Primary Thrombocythemia (01h Abstract in rivista)
    GIONA, FIORINA; GUARINO, MARIA LUISA; MARIANI, SABRINA
  • 11573/1397017 - 2020 - Cilostazol reduces cerebrovascular risk through the inhibition of multi-drug resistance protein 4/ATP binding cassette subfamily C member 4 (01a Articolo in rivista)
    PULCINELLI, FABIO MARIA; GUARINO, MARIA LUISA; MASSIMI, ISABELLA
  • 11573/789122 - 2015 - Kidney diseases (04f Poster)
    PRETAGOSTINI, RENZO; POLI, LUCA; SARGENTINI, VALERIA; GUARINO, MARIA LUISA; ANGELONI, ANTONIO; BERLOCO, PASQUALE BARTOLOMEO; BACHETONI ROSSI VACCARI, ALESSANDRA; D'ALESSANDRO, MARIADOMENICA
  • 11573/1440681 - 2020 - MRP4 over-expression has a role on both reducing nitric oxide-dependent antiplatelet effect and enhancing ADP induced platelet activation (01a Articolo in rivista)
    GUARINO, MARIA LUISA; MASSIMI, ISABELLA; ALEMANNO, LAURA; PULCINELLI, FABIO MARIA

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