Dottoressa di ricerca

ciclo: XXXIII


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

11573/1684632 - 2023 - Vascular liver diseases. A sex-oriented analysis of the literature
Zanetto, Alberto; Cossiga, Valentina; Shalaby, Sarah; Guarino, Maria; Invernizzi, Federica; Lapenna, Lucia; Becchetti, Chiara; Morisco, Filomena; Morelli, Maria Cristina; Merli, Manuela; Toniutto, Pierluigi; Burra, Patrizia - 01g Articolo di rassegna (Review)
rivista: DIGESTIVE AND LIVER DISEASE (-Roma: Editrice Gastroenterologica Italiana; Milano: Elsevier -Roma: Editrice Gastroenterologica Italiana. -Ospedaletto Pisa: Pacini) pp. 178-186 - issn: 1590-8658 - wos: WOS:000926219700001 (0) - scopus: 2-s2.0-85135171927 (0)

11573/1281896 - 2020 - Platelet activation and multidrug resistance protein-4 expression in children and adolescents with different subtypes of primary thrombocythemia
Giona, Fiorina; Massimi, Isabella; Guarino, Maria Luisa; Santopietro, Michelina; Laurino, Marica; Temperilli, Flavia; Palumbo, Giovanna; Foà, Robin; Pulcinelli, Fabio Maria - 01f Lettera, Nota
rivista: HAEMATOLOGICA (Fondaz Ferrata Storti:Strada Nuova 134, 27100 Pavia Italy:011 39 0382 531182, EMAIL:, Fax: 011 39 0382 27721) pp. e65-e67 - issn: 0390-6078 - wos: WOS:000510846700006 (1) - scopus: 2-s2.0-85078815707 (1)

11573/1440681 - 2020 - MRP4 over-expression has a role on both reducing nitric oxide-dependent antiplatelet effect and enhancing ADP induced platelet activation
Guarino, M. L.; Massimi, I.; Alemanno, L.; Conti, L.; Angiolillo, D. J.; Pulcinelli, F. M. - 01a Articolo in rivista
rivista: JOURNAL OF THROMBOSIS AND THROMBOLYSIS (Kluwer Academic Publishers:Journals Department, PO Box 322, 3300 AH Dordrecht Netherlands:011 31 78 6576050, EMAIL:,, INTERNET:, Fax: 011 31 78 6576254) pp. 1-8 - issn: 0929-5305 - wos: WOS:000559691200002 (6) - scopus: 2-s2.0-85089396515 (6)

11573/1397017 - 2020 - Cilostazol reduces cerebrovascular risk through the inhibition of multi-drug resistance protein 4/ATP binding cassette subfamily C member 4
Pulcinelli, F. M.; Guarino, M. L.; Massimi, I. - 01a Articolo in rivista
rivista: EXPERT OPINION ON PHARMACOTHERAPY (-London United Kingdom:Informa Healthcare -London , United Kingdom: Ashley Publications Limited) pp. 1-2 - issn: 1465-6566 - wos: WOS:000532037300001 (0) - scopus: 2-s2.0-85084251151 (0)

11573/1238243 - 2019 - Aspirin-dependent effects on purinergic P2Y1 receptor express
Massimi, Isabella; Alemanno, Laura; Guarino, Maria Luisa; Guerriero, Raffaella; Mancone, Massimo; Ceccacci, Andrea; Frati, Luigi; Angiolillo, Dominick J; Pulcinelli, Fabio M - 01a Articolo in rivista
rivista: THROMBOSIS AND HAEMOSTASIS (Stuttgart: Thieme Stuttgart: Schattauer) pp. 726-734 - issn: 0340-6245 - wos: WOS:000467408100007 (4) - scopus: 2-s2.0-85065176466 (4)

11573/1522021 - 2019 - Medicina di laboratorio - La diagnosi di malattia nel laboratorio clinico: collaborazione traduzione
Pulcinelli, Fabio Maria; Guarino, Maria Luisa; Pulcinelli, Francesca Maria - 02e Traduzione in volume
libro: Medicina di laboratorio - Michael Laposata ()

11573/1078271 - 2018 - Impact of Multidrug Resistance Protein-4 Inhibitors on Modulating Platelet Function and High on-Aspirin Treatment Platelet Reactivity
Alemanno, Laura; Massimi, Isabella; Klaus, Vanessa; Guarino, Maria Luisa; Maltese, Teresa; Frati, Luigi; Angiolillo, Dominick J.; Pulcinelli, Fabio M. - 01a Articolo in rivista
rivista: THROMBOSIS AND HAEMOSTASIS (Stuttgart: Thieme Stuttgart: Schattauer) pp. 490-501 - issn: 0340-6245 - wos: WOS:000427285600007 (10) - scopus: 2-s2.0-85042173467 (12)

11573/1100816 - 2018 - MiR-21 role in aspirin-dependent PPARα and MRP4 up-regulation
Massimi, I.; Alemanno, Laura; Guarino, M. L.; Guerriero, R.; Frati, L.; Biasucci, L.; Pulcinelli, Fm - 01a Articolo in rivista
rivista: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS (Hoboken NJ : John Wiley & Sons Inc.) pp. 596-606 - issn: 2475-0379 - wos: WOS:000452488100021 (5) - scopus: 2-s2.0-85054480759 (6)

11573/1230556 - 2018 - Non-steroidal anti-inflammatory drugs increase MRP4 expression in an endometriotic epithelial cell line in a PPARa dependent manner
Massimi, I; Pulcinelli, Fm; Piscitelli, Valerio Piacentino; Alemanno, L; Maltese, T; Guarino, Ml; Marci, R; Canny, Go; Frati, L; Mallozzi, M; Frega, A; Caserta, D. - 01a Articolo in rivista
rivista: EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES (Roma: Verduci publisher.) pp. 8487-8496 - issn: 1128-3602 - wos: WOS:000453456200052 (4) - scopus: 2-s2.0-85058621827 (6)

11573/956293 - 2017 - New platelet functional method for identification of pathogenic antibodies in HIT patients
Guarino, Maria Luisa; Massimi, Isabella; Mardente, Stefania; Lappa, A.; Donfrancesco, S.; Visentin, G. P.; Pulcinelli, Fabio Maria - 01a Articolo in rivista
rivista: PLATELETS (Basingstoke, United Kingdom: CARFAX Publishing Limited) pp. 728-730 - issn: 0953-7104 - wos: WOS:000415623600014 (9) - scopus: 2-s2.0-85015034814 (10)

11573/789122 - 2015 - Kidney diseases
Pretagostini, Renzo; Poli, Luca; Sargentini, Valeria; Guarino, Maria Luisa; Angeloni, Antonio; Berloco, Pasquale Bartolomeo; Bachetoni Rossi Vaccari, Alessandra; D'alessandro, Mariadomenica - 04f Poster
rivista: CLINICAL CHEMISTRY AND LABORATORY MEDICINE (Berlin; New York: de Gruyter.) pp. S1070-S1070 - issn: 1437-4331 - wos: (0) - scopus: (0)
congresso: 21 IFCC-EFLM European Congress of Clinical Chemistry and Laboratori Medicine (Paris)

11573/787521 - 2015 - Nonsteroidal anti-inflammatory drugs in-vitro and in-vivo treatment and Multidrug Resistance Protein 4 expression in human platelets
Temperilli, Flavia; Di Franco, Manuela; Massimi, Isabella; Guarino, Maria Luisa; Guzzo, Maria Paola; Frati, Luigi; Pulcinelli, Fabio Maria; Valesini, Guido - 01a Articolo in rivista
rivista: VASCULAR PHARMACOLOGY (Elsevier Science Limited:Oxford Fulfillment Center, PO Box 800, Kidlington Oxford OX5 1DX United Kingdom:011 44 1865 843000, 011 44 1865 843699, EMAIL:,, INTERNET:,, Fax: 011 44 1865 843010) pp. 11-17 - issn: 1537-1891 - wos: WOS:000368211800002 (19) - scopus: 2-s2.0-84961194034 (19)

11573/689461 - 2015 - Arachidonic acid-stimulated platelet tests: Identification of patients less sensitive to aspirin treatment
Temperilli, Flavia; Rina, A.; Massimi, Isabella; Montemari, A. L.; Guarino, M. L.; Zicari, Alessandra; Pulcinelli, Fabio Maria - 01a Articolo in rivista
rivista: PLATELETS (Basingstoke, United Kingdom: CARFAX Publishing Limited) pp. 783-787 - issn: 0953-7104 - wos: WOS:000369892400012 (14) - scopus: 2-s2.0-84942982926 (15)

11573/1284892 - 2014 - MRP4 Expression and Platelet Activation in Children and Adolescents with Different Subtypes of Primary Thrombocythemia
Giona, F; Laurino, M; Massimi, I; Guarino, Ml; Temperilli, F; Palumbo, G; Mariani, S; Marzella, D; Foà, R. And Pulcinelli Fm. - 01h Abstract in rivista
rivista: BLOOD (New York: Elsevier Inc. [Washington DC etc.]: American Society of Hematology) pp. - - issn: 0006-4971 - wos: WOS:000349242702057 (0) - scopus: (0)

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