Alloatti, Giuseppe

Angelone, T.

Cerra, M. C. C.

De Cindio, B.

Femmin&#242

Lupi, F.

Pagliaro, Pasquale

Penna, Claudia

Quintieri, Anna Maria

Tullio, Francesca

English

Femminò, Saveria

Quintieri, ANNA MARIA

Institutional Research Information System University of Turin

clinical application of β-blocker agents requires patient and diseaseoriented approaches.doi:10.1016/j.vph.2015.11.029Is NLRP3 inflammasome a new pharmacological target inmyocardial ischemia/reperfusion injury?S. Femminòa,, F. Chiazzab, R. Mastrocolaa, F. Tullioa, C. Pennaa,D. Nigroa, G. Alloattic, M. Coccob, D. Garellab, M. Bertinariab,R. Fantozzib, M. Aragnoa, M. Collinob, P. PagliaroaaDepartment of Clinical and Biological Sciences, University of Turin, ItalybDepartment of Drug Science and Technology, University of Turin, ItalycDepartment of Life Sciences and Systems Biology, University of Turin,ItalyObjectives: Recently it has been documented that the NLRP3inflammasome plays a pivotal role in the inflammatory responseto tissue injury. The NLRP3 inflammasome is a large multimericdanger-sensing platform that induces activation of the caspase-1 andmediates the cleavage of inactive pro-IL-1β, among other proteins,into its active form. We have shown that the activation of the NLRP3inflammasome exacerbates myocardial ischemia/reperfusion (I/R)injury in diabetic mice. Moreover, our group previously demonstratedthat INF-4E inhibits NLRP3, ATPase and caspase-1 activities in THP-1cells. Here we test in an ex-vivo model whether INF-4E inhibitingNLRP3 may positively affect I/R injury, post-ischemic cardiac functionand molecular response in the rat hearts.Materials and methods: Isolated hearts from male Wistar rats(bodyweight 450,550 g; n = 7) underwent perfusionwithout ischemia(Sham) or I/R (30-min ischemia plus 20-min or 60 min reperfusion)with and without IFN-4E treatment (50 M for 20-min before ischemia).Coronary perfusion pressure and left ventricular pressure (LVP) weremonitored, and dP/dtmax assessed during the entire period ofperfusion. Biopsies obtained at the end of reperfusion were used forWestern blotting evaluations of NLRP3 and caspase-1 (apoptosis index)levels/activities and for assessment of RISK pathway involvement. Atthe end of 60 min reperfusion infarct size was measured with nitro-blue-tetrazolium technique by an independent observer.Results: In this preliminary study, the 20 min IFN-4E pre-ischemicadministration induced a significant reduction of infarct size and animprovement in post-ischemic LVP recovery. Western blot analysisdemonstrated NLRP3 and caspase-1 activation by I/R procedure,which were strongly attenuated after IFN-4E pre-treatment. More-over, an important modulation of RISK kinase phosphorylation wasobserved, though a clear-cut correlation between the reduction ininfarct size and phosphorylation of RISK kinases was not observed.Conclusions: These preliminary results demonstrate that the IFN-4E inhibits the formation of the NLRP3 inflammasome in the rat heartand ameliorates the response to myocardial I/R injury, confirming theability of this drug to affect NLRP3 inflammasome complex activation.doi:10.1016/j.vph.2015.11.030Spread bio oil diet and cardiac response to ischemia/reperfusion:A preliminary study in miceF. Tullioa,, S. Femminòa, G. Alloattib, T. Angelonec, M.C.C. Cerrab,B. De Cindiod, F. Lupid, A.M. Quintierib, P. Pagliaroa, C. PennaaaDepartment of Clinical and Biological Sciences, ItalybDepartment of Life Sciences Systems Biology, University of Turin, Turin,ItalycDepartment of Biology, Ecology and Earth Science, ItalydDepartment of Information,Modeling, Electronics and System Engineering(D.I.M.E.S.), University of Calabria, Arcavacata di Rende (CS), ItalyObjectives: The role of diet is of paramount importance in theprevention and development of cardiovascular disease (CVD). A diethigh in saturated fat increases the risk of heart disease and stroke,in particular it causes about 31% of coronary heart disease and 11%of stroke worldwide. The Mediterranean diet is the symbol of theItalian style and is considered able to reduce the burden of CVD, butthis protective alimentary modality is frequently neglected forincorrect life style. Recently it has been suggested that “spread biooil” (SBO), an innovative food product, at hard fat phase, mainlybased on olive oil, may be beneficial, thus in the present study weaimed to compare three different diets, standard, high fat and SBOdiet, in terms of cardiac response to the ischemia/reperfusion (I/R).Materials and methods: Male mice were fed with standard diet(SD), high fat (HF) or spread SBO diet for 4 weeks. Before, during andat the end of these diets blood samples were collected and theanthropometric parameters, such as body mass index (BMI), weight,height and abdominal circumference, were evaluated. The heartsof each group were randomly assigned to two different protocols:only Tyrode perfusion (Sham) or I/R (30 min ischemia and 60 minreperfusion), at the end of experiments the infarct size was evaluatedwith nitro-blue tetrazolium techniques.Results: While HF diet did not induce significant variations ofanthropometric parameters (BMI, weight, and abdominal circumfer-ence), left ventricular weight resulted significantly higher in compar-ison to SD animals. Also, the infarct size resulted higher in HF than in SDhearts (infarct size 65 ± 5% and 43 ± 5%, respectively). Although, theanimals fed with SBO diet displayed a significant increase of abdominalcircumferencewith respect to SD only, surprisingly enough, their heartshad a smaller infarct size (26 ± 6%) with respect to both SD and HFanimals.Conclusions: These preliminary data suggest that the SBO increasesthe resistance of heart to I/R challenge, despite partial modificationsof anthropometric parameters. To explain these preliminary resultsfurther investigations and analyses of cardioprotective pathways arenecessary.doi:10.1016/j.vph.2015.11.031Obestatin exerts post-conditioning-like cardioprotective effectsvia nitrosative/oxidative signalingC. Pennaa,, G. Alloattib, T. Angeloned, M.C. Cerrad, S. Femminòa,M.P. Gallob, E. Ghigoc, P. Pagliaroa, C. Roccad, F. Tullioa,L. Trovatoc, R. GranatacaDepartment of Clinical and Biological Sciences, ItalybDepartment of Life Sciences and Systems Biology, ItalycDepartment of Medical Sciences, University of Turin, Turin, ItalydDepartment of Biology, Ecology and Earth Science, University of Calabria,Arcavacata di Rende (CS), ItalyObjectives: Obestatin (Obe), a 23-amino acid peptide derivedfrom preproghrelin, affects several neurometabolic and cardiacphysiological functions. A preconditioning-like effect of obestatin inlimiting apoptosis and ischemia/reperfusion (I/R) injury in bothisolated rat heart and cultured adult cardiomyocytes has been recentlydemonstrated. We hypothesized an obestatin-postconditioning-likecardioprotective effect via a nitrosative/oxidative mitochondrialsignaling (NO/ROS/PKCε/mitoKATP channel).Materials and methods: Isolated hearts underwent the followingprotocols: control group (I/R, 30 min global ischemia followed by120 min reperfusion); Obe group (obestatin 75 nM, for 20 min imme-diately after ischemia and 100 min reperfusion). Other hearts receivedobestatin plus different antagonist of NO/ROS/PKCε/mitoKATP channelpathway. Each inhibitor was given during the last 5 min of stabilizationand the initial 20 min reperfusion. Developed left ventricular pressureAbstracts 51

Spread bio oil diet and cardiac response to ischemia/reperfusion: A preliminary study in mice

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Spread bio oil diet and cardiac response to ischemia/reperfusion: A preliminary study in mice

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