Laboratorio di Cardio and Neurovascular Pathophysiology

Laboratorio di Cardio and Neurovascular Pathophysiology
Responsabile: Prof. Giuseppe Lembo

Il Laboratorio di Cardio and Neurovascular Pathophysiology ha sede presso il Polo Molise dell’Università “Sapienza” di Roma, ovvero presso l’IRCCS Neuromed di Pozzilli (IS), grazie ad apposita convenzione stipulata tra le parti.

Il Laboratorio comprende anche la seguente Unità di Ricerca:

Immunologia cardiovascolare
Responsabile: dott.ssa Daniela Carnevale.

Principali linee di ricerca Prof. Lembo

  • Basi cardio e neurovascolari delle malattie neurodegenerative e delle demenze di tipo Alzheimer.
  • Ruolo delle proteine della matrice extracellulare nella modulazione della via di segnalazione del TGFbcome meccanismo di regolazione della funzione vascolare e della pressione arteriosa.
  • Meccanismi molecolari delle cellule muscolari lisce rilevanti negli aneurismi dell’aorta.
  • Ruolo di fattori di trascrizione cruciali per il differenziamento embrionale neuro- vs cardio-specifico, nei processi di riparazione tissutale in seguito ad ischemia miocardica.


Progetti di ricerca finanziati (anni 2012-2017)
Responsabile scientifico: Giuseppe Lembo

2017. PI del Programma di Ricerca Scientifica PRIN 2015 (MIUR) “Characterization of adaptive or maladaptive influences of innate immune system on cardiac hypertrophic remodeling in response to pressure overload.”

2014-2017. Responsabile Scientifico del progetto PON03PE_00060_7 “Sviluppo preclinico di nuove terapie e di strategie innovative per la produzione di molecole ad azione farmacologica”, nell’ambito del Programma Operativo Nazionale PON Ricerca e Competitività 2007-2013.

2013. Coordinatore Scientifico del Programma di Ricerca “Caratterizzazione di nuovi target genetico-molecolari nella parete vascolare dell’uomo” finanziato dalla Regione Molise nell’ambito del PSN 2006-2008.

2013-2016. PI e Coordinatore Nazionale del Programma di Ricerca Scientifica PRIN 2010-2011 (MIUR) “Nuove interazioni tra pathways molecolari favorenti un rimodellamento cardiaco adattativo nella cardiomiopatia da sovraccarico”.

2013-2015. PI del Progetto Award “Cognitive dysfunction in carotid stenosis: determinants and therapeutical opportunities”, finanziato nell’ambito della Ricerca Scientifica 2013, Università “Sapienza” di Roma.

2012-2015. Responsabile di Unità Operativa nel progetto “MOdelli in VIvo di Patologie umanE - MOVIE”, nell’ambito del Programma Operativo Regionale POR Campania 2007/2013.

2012-2015. Responsabile di Unità Operativa nel progetto “Biotecnologie integrate per terapie innovative e personalizzate di malattie oncologiche e cardiovascolari – OCKEY”, nell’ambito del Programma Operativo Regionale POR Campania 2007/2013.

2011-2015. Responsabile Scientifico del progetto PON01_01227 “SIRT-in: sviluppo di modulatori delle Sirtuine come nuovo approccio terapeutico nelle patologie neurodegenerative, oncologiche e cardiovascolari” nell’ambito del Programma Operativo Nazionale PON Ricerca e Competitività 2007-2013.

2011-2015. Responsabile di Unità Operativa nel progetto PON01_00829 “Piattaforme tecnologiche innovative per l’ingegneria tissutale” nell’ambito del Programma Operativo Nazionale PON Ricerca e Competitività 2007-2013.

2011-2015. Responsabile di Unità Operativa nel Progetto FIRB-MERIT “Approccio integrato clinico e sperimentale allo studio dell’invecchiamento cerebrale e delle malattie neurodegenerative: basi molecolari, epidemiologia genetica, neuroimaging multimodale e farmacogenetica”.

2011-2013. Responsabile del Progetto "Utilizzo della microscopia confocale per la caratterizzazione di molecole responsabili del legame fisiopatologico tra infiammazione ed ipertensione arteriosa", finanziato nell’ambito del programma di Acquisizione di medie e grandi attrezzature scientifiche dell’Università “Sapienza” di Roma.

2011-2012. Responsabile Progetto “Caratterizzazione dei meccanismi molecolari del decadimento cognitivo riconducibile alla malattia di Alzheimer nell’ipertensione arteriosa” finanziato dalla Società Italiana dell’Ipertensione Arteriosa (SIIA).

2010-2012. Responsabile del Progetto "Imaging in vivo su piccoli animali per la caratterizzazione degli effetti di terapie cellulari", finanziato nell’ambito del programma di Acquisizione di medie e grandi attrezzature scientifiche dell’Università “Sapienza” di Roma.

2010-2012. Responsabile di Unità Operativa nel Progetto PRIN “Terapia genica con melusina in modelli animali di insufficienza cardiaca”, finanziato dal Ministero dell’Università e della Ricerca.

Pubblicazioni più rilevanti (anni 2012-1017)
Responsabile: Prof. Giuseppe Lembo

Maffei A, Cifelli G, Carnevale R, Iacobucci R, Pallante F, Fardella V, Fardella S, Hirsch E, Lembo G, Carnevale D. PI3KγInhibition Protects Against Diabetic Cardiomyopathy in Mice. Rev Esp Cardiol (Engl Ed). 2017 Jan;70(1):16-24.

Perrotta M, Lembo G, Carnevale D The Multifaceted Roles of PI3K  in Hypertension, Vascular Biology, and Inflammation, Int. J. Mol. Sci. 2016, 17, 1858; doi:10.3390/ijms17111858.

Carnevale D, Perrotta M, Pallante F, Fardella V, Iacobucci R, Fardella S, Carnevale L, Carnevale R, De Lucia M, Cifelli G, Lembo G, A Cholinergic-Sympathetic Pathway primes Immunity in Hypertension and Mediates Brain-To-Spleen Communication, Nat Commun. 2016 Sep 27;7:13035. doi: 10.1038/ncomms13035.

Maffei A, Di Mauro V, Catalucci D, Lembo G. MiR-153/Kv7.4: a novel molecular axis in the regulation of hypertension. Cardiovasc Res. 2016 Sep 15. pii: cvw208. [Epub ahead of print] PubMed PMID: 27635057.

Landolfi A, Selvetella G, Cugino D, Grillea G, Maffei A, Notte A, Lembo G, Carnevale D. Hemorrhagic transformation of acute ischemic stroke is limited in hypertensive patients with cardiac hypertrophy. Int J Cardiol. 2016 Sep 15;219:362-6. doi: 10.1016/j.ijcard.2016.06.060. Epub 2016 Jun 23.

Lembo G, Grassi G. Flavanol-rich cocoa at breakfast: the right remedy after a sleepless night to prevent negative effects on blood pressure and cognition? J Hypertens. 2016 Jul;34(7):1252-3.

Cohen AT, Harrington RA, Goldhaber SZ, Hull RD, Wiens BL, Gold A, Hernandez AF, Gibson CM; APEX Investigators. Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients. N Engl J Med. 2016 Aug 11;375(6):534-44. doi: 10.1056/NEJMoa1601747. PubMed PMID: 27232649.

Carnevale D, Lembo G. Immunological Aspects of Hypertension. High Blood Press Cardiovasc Prev. 2016 Jun;23(2):91-5. doi: 10.1007/s40292-016-0141-8. PubMed PMID: 27080378.

McMurray JJ, Krum H, Abraham WT, Dickstein K, Køber LV, Desai AS, Solomon SD, Greenlaw N, Ali MA, Chiang Y, Shao Q, Tarnesby G, Massie BM; ATMOSPHERE Committees Investigators. Aliskiren, Enalapril, or Aliskiren and Enalapril in Heart Failure. N Engl J Med. 2016 Apr 21;374(16):1521-32.

Perrotta M, Lembo G, Carnevale D. Hypertension and Dementia: Epidemiological and Experimental Evidence Revealing a Detrimental Relationship. Int J Mol Sci. 2016 Mar 8;17(3).

Redon J, Pichler G; Missed Dose Study Group. Comparative study of the efficacy of olmesartan/amlodipine vs. perindopril/amlodipine in peripheral blood pressure after missed dose in type 2 diabetes. J Hypertens. 2016 Feb;34(2):359-67.

Kristensen SL, Preiss D, Jhund PS, Squire I, Cardoso JS, Merkely B, Martinez F, Starling RC, Desai AS, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR, McMurray JJ, Packer M; PARADIGM-HF Investigators and Committees. Risk Related to Pre-Diabetes Mellitus and Diabetes Mellitus in Heart Failure With Reduced Ejection Fraction: Insights From Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial. Circ Heart Fail. 2016 Jan;9(1).

Mancia G, Omboni S, Chazova I, Coca A, Girerd X, Haller H, Parati G, Pauletto P, Pupek-Musialik D, Svyshchenko Y; FELT Study Group. Effects of the lercanidipine-enalapril combination vs. the corresponding monotherapies on home blood pressure in hypertension: evidence from a large database. J Hypertens. 2016 Jan;34(1):139-48.

Stöhr R, Kappel BA, Carnevale D, Cavalera M, Mavilio M, Arisi I, Fardella V, Cifelli G, Casagrande V, Rizza S, Cattaneo A, Mauriello A, Menghini R, Lembo G, Federici M. TIMP3 interplays with apelin to regulate cardiovascular metabolism in hypercholesterolemic mice. Mol Metab. 2015 Aug 6;4(10):741-52.

Carnevale D, Lembo G. PlGF, immune system and hypertension. Oncotarget. 2015 Jul 30;6(21):18246-7.

Carnevale D, Perrotta M, Lembo G, Trimarco B. Pathophysiological Links Among Hypertension and Alzheimer's Disease. High Blood Press Cardiovasc Prev. 2015 Jun.

Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Peterson ED, Holman RR; TECOS Study Group. “Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes”. N Engl J Med. 2015 Jul 16;373(3):232-42.

D'Andrea I, Fardella V, Fardella S, Pallante F, Ghigo A, Iacobucci R, Maffei A, Hirsch E, Lembo G, Carnevale D. Lack of kinase-independent activity of PI3Kγin locus coeruleus induces ADHD symptoms through increased CREB signaling. EMBO Mol Med. 2015 Apr 16;7(7):904-17.

Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, Stroes ES, Langslet G, Raal FJ, El Shahawy M, Koren MJ, Lepor NE, Lorenzato C, Pordy R,Chaudhari U, Kastelein JJ; ODYSSEY LONG TERM Investigators. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015 Apr 16;372(16):1489-99.

Packer M, McMurray JJ, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile M, Andersen K, Arango JL, Arnold JM, Bělohlávek J, Böhm M, Boytsov S, Burgess LJ, Cabrera W, Calvo C, Chen CH, Dukat A, Duarte YC, Erglis A, Fu M, Gomez E, Gonzàlez-Medina A, Hagège AA, Huang J, Katova T, Kiatchoosakun S, Kim KS, Kozan Ö, Llamas EB, Martinez F, Merkely B, Mendoza I, Mosterd A, Negrusz-Kawecka M, Peuhkurinen K, Ramires FJ, Refsgaard J, Rosenthal A, Senni M, Sibulo AS Jr, Silva-Cardoso J, Squire IB, Starling RC, Teerlink JR, Vanhaecke J, Vinereanu D, Wong RC; PARADIGM-HF Investigators and Coordinators. Angiotensin receptor neprilysin inhibition compared with enalapril on the risk of clinical progression in surviving patients with heart failure. Circulation. 2015 Jan 6;131(1):54-61.

Carnevale D, Pallante F, Fardella V, Fardella S, Iacobucci R, Federici M, Cifelli G, De Lucia M, Lembo G. PlGF mediates a neuroimmune interaction in the spleen to allow the onset of hypertension. Immunity. 2014 Nov 20;41(5):737-52.

Perino A, Beretta M, Kilić A, Ghigo A, Carnevale D, Repetto IE, Braccini L, Longo D, Liebig-Gonglach M, Zaglia T, Iacobucci R, Mongillo M, Wetzker R, Bauer M, Aime S, Vercelli A, Lembo G, Pfeifer A, Hirsch E. Combined inhibition of PI3Kβ and PI3Kγ reduces fat mass by enhancing α-MSH-dependent sympathetic drive. Sci Signal. 2014 Nov 18;7(352):ra110.

Virdis A, Savoia C, Grassi G, Lembo G, Vecchione C, Seravalle G, Taddei S, Volpe M, Rosei EA, Rizzoni D. Evaluation of microvascular structure in humans: a 'state-of-the-art' document of the Working Group on Macrovascular and Microvascular Alterations of the Italian Society of Arterial Hypertension. J Hypertens. 2014 Nov;32(11):2120-9

McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004.

Arcaro A, Lembo G, Tocchetti CG. Nitroxyl (HNO) for treatment of acute heart failure. Curr Heart Fail Rep. 2014 Sep;11(3):227-35.

Reboldi G, Angeli F, de Simone G, Staessen JA, Verdecchia P; Cardio-Sis Investigators. Tight versus standard blood pressure control in patients with hypertension with and without cardiovascular disease. Hypertension. 2014 Mar;63(3):475-82.

Maggioni AP, Greene SJ, Fonarow GC, Böhm M, Zannad F, Solomon SD, Lewis EF, Baschiera F, Hua TA, Gimpelewicz CR, Lesogor A, Gheorghiade M; ASTRONAUT Investigators and Coordinators. Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial. Eur Heart J. 2013 Oct;34(40):3117-27.

Dunkler D, Dehghan M, Teo KK, Heinze G, Gao P, Kohl M, Clase CM, Mann JF, Yusuf S, Oberbauer R; ONTARGET Investigators. Diet and kidney disease in high-risk individuals with type 2 diabetes mellitus. JAMA Intern Med. 2013 Oct 14;173(18):1682-92.

Carnevale D, Lembo G. G-protein-coupled receptor kinases in hypertension. High Blood Press Cardiovasc Prev. 2013 Mar;20(1):3-4.

McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau J, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Committees and Investigators. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF). Eur J Heart Fail. 2013 Sep;15(9):1062-73.

Gheorghiade M, Böhm M, Greene SJ, Fonarow GC, Lewis EF, Zannad F, Solomon SD, Baschiera F, Botha J, Hua TA, Gimpelewicz CR, Jaumont X, Lesogor A, Maggioni AP; ASTRONAUT Investigators and Coordinators. Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: the ASTRONAUT randomized trial. JAMA. 2013 Mar 20;309(11):1125-35.

Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, Chaturvedi N, Persson F, Desai AS, Nicolaides M, Richard A, Xiang Z, Brunel P, Pfeffer MA; ALTITUDE Investigators. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012 Dec 6;367(23):2204-13.

Carnevale D, Lembo G. Placental Growth Factor and Cardiac Inflammation. Trends Cardiovasc Med. 2012 Nov;22(8):209-12.

Litteri G, Carnevale D, D'Urso A, Cifelli G, Braghetta P, Damato A, Bizzotto D, Landolfi A, Da Ros F, Sabatelli P, Facchinello N, Maffei A, Volpin D, Colombatti A, Bressan GM, Lembo G. Vascular Smooth Muscle Emilin-1 Is a Regulator of Arteriolar Myogenic Response and Blood Pressure. Arterioscler Thromb Vasc Biol. 2012 Sep;32(9):2178-84.

Carnevale D, Mascio G, D'Andrea I, Fardella V, Bell RD, Branchi I, Pallante F, Zlokovic B, Yan SS, Lembo G. Hypertension Induces Brain β-Amyloid Accumulation, Cognitive Impairment, and Memory Deterioration Through Activation of Receptor for Advanced Glycation End Products in Brain Vasculature. Hypertension. 2012 Jul;60(1):188-97. Epub 2012 May 21.

Carnevale D, Lembo G. PI3Kγin hypertension: a novel therapeutic target controlling vascular myogenic tone and target organ damage. Cardiovasc Res. 2012 Jul 10. [Epub ahead of print]

Omboni S, Malacco E, Mallion JM, Volpe M, Zanchetti A; Study Group. Twenty-four hour and early morning blood pressure control of olmesartan vs. ramipril in elderly hypertensive patients: pooled individual data analysis of two randomized, double-blind, parallel-group studies. J Hypertens. 2012 Jul;30(7):1468-77.

Carnevale D, Vecchione C, Mascio G, Esposito G, Cifelli G, Martinello K, Landolfi A, Selvetella G, Grieco P, Damato A, Franco E, Haase H, Maffei A, Ciraolo E, Fucile S, Frati G, Mazzoni O, Hirsch E, Lembo G. PI3Kγinhibition reduces blood pressure by a vasorelaxant Akt/L-type calcium channel mechanism. Cardiovasc Res. 2012 Jan 1;93(1):200-9.

Punthakee Z, Bosch J, Dagenais G, Diaz R, Holman R, Probstfield JL, Ramachandran A, Riddle MC, Rydén LE, Zinman B, Afzal R, Yusuf S, Gerstein HC; TIDE Trial Investigators. Design, history and results of the Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) randomised controlled trial. Diabetologia. 2012 Jan;55(1):36-45.