Ciro Indolfi

Publications (57)340.72 Total impact

• Article: Renal Sympathetic Denervation for Treating Resistant Hypertension.

  Alberto Polimeni, Antonio Curcio, Ciro Indolfi
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  ABSTRACT: Systemic hypertension represents a significant global concern, because it contributes to vascular and renal morbidity, cardiovascular mortality, and economic burden, hence the impact of hypertension is a major issue in public health worldwide. Improving high blood pressure management is therefore fundamental to influencing clinical outcomes. Despite adherence to multiple available medical therapies, a significant proportion of patients has persistent blood pressure elevation, a condition termed "resistant hypertension". Renal sympathetic innervations contribute to lack of response of anti-hypertensive drugs through an imbalance of regulatory mechanisms. Renal afferent nerve fibers are responsible for sympathetic activation and contribute to blood pressure homeostasis while afferent signals from the kidneys are integrated at the central nervous system and enhance sympathetic nerve discharge. In this regard, a novel strategy that selectively removes these hypertensive contributors represents a new therapeutic opportunity. Recently, a catheter-based method to induce renal sympathetic denervation has been introduced into daily practice. Clinical evaluation of selective renal sympathetic denervation demonstrated a decrease of renal norepinephrine spillover and renin activity, an increase of renal plasma flow, and has confirmed clinically significant, sustained reductions in blood pressure in patients with resistant hypertension. This review summarizes the available data on the role of sympathetic activation in the pathophysiology of hypertension and the current concepts in transcatheter renal artery ablation with radiofrequency delivery for systemic hypertension. Suggestions regarding targets for future systemic hypertension management are also described.
  Circulation Journal 03/2013; · 3.77 Impact Factor
• Article: Vascular miRNAs After Balloon Angioplasty.

  Alberto Polimeni, Salvatore De Rosa, Ciro Indolfi
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  ABSTRACT: MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression through translational repression or degradation of the target mRNA. Available strategies to improve stent patency lead to the risk of potential stent thrombosis. Modulation of miRs could be a promising means of reducing VSMC proliferation while increasing endothelial regeneration at the same time. Therefore, the goal of this review is to summarize recent experimental evidences on the role played by miRNAs in vascular remodeling, and particularly on VSMC phenotype switch and in endothelial cells, in response to vascular injury.
  Trends in cardiovascular medicine 01/2013; 23(1):9-14. · 4.37 Impact Factor
• Article: Intracoronary abciximab reduces death and major adverse cardiovascular events in acute coronary syndromes: A meta-analysis of clinical trials.

  Salvatore De Rosa, Gianluca Caiazzo, Daniele Torella, Ciro Indolfi
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  ABSTRACT: BACKGROUND: Successful reperfusion of epicardial coronary arteries does not necessarily result in actual myocardial perfusion. Local intracoronary (IC) delivery of GP IIb/IIIa inhibitors (GPI) has been proposed to achieve further clinical efficacy when compared to standard intravenous (IV) administration. However clinical trials have shown conflicting results. The aim of the present study was to compare IC with IV abciximab administration on mortality and MACEs in patients with ACS undergoing PCI. METHODS: We performed a meta-analysis of all available clinical trials comparing intracoronary versus intravenous abciximab administration. RESULTS: At short-term analysis, incidence of MACEs was significantly lower in the IC group than in the IV group (OR=0.56; 95% CI 0.35-0.89; p=0.015). Interestingly, subgroup analysis showed that most benefit was coming from those studies with a main baseline LVEF<50% (OR=0.33 95% CI 0.18-0.59). Similarly, long-term incidence of MACEs was significantly lower in the IC group than in the IV group (OR=0.47; 95% CI 0.31-0.71; p<0.001), with most benefit coming from those studies enrolling patients with a main baseline EF<50% (OR=0.38 95% CI 0.23-0.63 p<0.001). In addition, long-term incidence of death was also lower in the IC group than in the IV group (OR=0.42; 95% CI 0.20-0.86; p=0.009). CONCLUSIONS: Our meta-analysis provides evidence of a net clinical benefit for intracoronary versus intravenous abciximab administration, with the highest benefit observed in high-risk ACS patients, such as those with reduced baseline LVEF.
  International journal of cardiology 12/2012; · 7.08 Impact Factor
• Article: Inhibition of miR-92a increases endothelial proliferation and migration in vitro as well as reduces neointimal proliferation in vivo after vascular injury.

  Claudio Iaconetti, Alberto Polimeni, Sabato Sorrentino, Jolanda Sabatino, Gianluigi Pironti, Giovanni Esposito, Antonio Curcio, Ciro Indolfi
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  ABSTRACT: The role of miR-92a on vascular remodelling after injury is currently unknown. Thus, the aim of the present study was to evaluate the role of miR-92a on rat endothelial and vascular smooth muscle cells proliferation and migration in vitro as well as after balloon injury or arterial stenting in vivo. MiR-92a was highly expressed in RAO-ECs and vascular endothelium, but not in RAO-SMCs or medial smooth muscle as assessed by real-time RT-PCR. Importantly, BrdU incorporation and wound healing assay provide evidence that functional inhibition of miR-92a resulted in an increased RAO-ECs proliferation and migration, but had no effect on RAO-SMCs proliferation or migration in vitro. Immunoblotting analysis revealed an increased phosphorylation of ERK1/2, JNK/SAPK as well as eNOS and phospho-eNOS increased expression level in RAO-ECs as a consequence of miR-92a inhibition. Using gain and loss of function experiments, we showed that miR-92a modulates regulation of KLF4 and MKK4 expression level in endothelial cells. Finally, in vivo administration of antagomiR-92a significantly enhanced re-endothelialization in injured carotid arteries and reduced neointimal formation after balloon injury or arterial stenting. These data provide the first evidence that inhibition of miR-92a may represent a novel strategy to improve endothelial regeneration and reduce restenosis after vascular injury.
  Archiv für Kreislaufforschung 09/2012; 107(5):296. · 7.35 Impact Factor
• Article: Effects of successful percutaneous lower extremity revascularization on cardiovascular outcome in patients with peripheral arterial disease.

  Giuseppe Giugliano, Luigi Di Serafino, Cinzia Perrino, Vittorio Schiano, Eugenio Laurenzano, Salvatore Cassese, Mario De Laurentis, Gabriele Giacomo Schiattarella, Linda Brevetti, Anna Sannino, Giuseppe Gargiulo, Anna Franzone, Ciro Indolfi, Federico Piscione, Bruno Trimarco, Giovanni Esposito
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  ABSTRACT: BACKGROUND: Lower extremity peripheral arterial disease (LE-PAD) reduces walking capacity and is associated with an increased cardiovascular risk. Endovascular revascularization of LE-PAD improves walking performance and quality of life. In the present study, we determined whether successful lower limbs revascularization also impacts cardiovascular outcome in LE-PAD patients. METHODS: 479 consecutive LE-PAD patients at stage II of Fontaine's classification, with ankle/brachial index ≤0.90 and one or more stenosis >50% in at least one leg artery, were enrolled in the study. According to the Trans-Atlantic Inter Society Consensus II recommendations, 264 (55.1%) underwent percutaneous lower extremity angioplasty (PTA group), while 215 (44.9%) were managed with conservative therapy (MT group). The incidence of major cardiovascular events (including cardiovascular death, myocardial infarction, ischemic stroke, coronary and carotid revascularizations) was prospectively analyzed by Kaplan-Meier curves. Crude and adjusted HRs (95% CI) of developing a cardiovascular event were calculated by Cox analysis. RESULTS: No baseline differences were observed among the groups, except for a lower maximum walking distance in the PTA group. During a median follow-up of 21months (12.0-29.0), the incidence of cardiovascular events was markedly lower in PTA compared to MT patients (6.4% vs. 16.3%; p=0.003), and patients in the MT group showed a 4.1-fold increased cardiovascular risk compared to patients in the PTA group, after adjustment for potential confounders (95% CI 1.22-13.57, p=0.023). CONCLUSIONS: This study shows that successful revascularization of LE-PAD patients affected by intermittent claudication, in addition to improving functional status, reduces the occurrence of future major cardiovascular events.
  International journal of cardiology 07/2012; · 7.08 Impact Factor
• Article: High sensitive troponin T in individuals with chest pain of presumed ischemic origin.

  Giovanni Cuda, Margherita Lentini, Luigia Gallo, Fortunata G Lucia, Lorenzina Giacinto Carinci, Serafina Mancuso, Rosa A Biondi, Raffaella Sinopoli, Rita Casadonte, Pietro H Guzzi, Mario Cannataro, Annalisa Mongiardo, Claudio Iaconetti, Angela Bochicchio, Antonio Curcio, Daniele Torella, Pietroantonio Ricci, Ciro Indolfi, Francesco Costanzo
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  ABSTRACT: This study was aimed at assessing the bias of high sensitive cardiac troponin T vs. the standard cardiac troponin T in a selected population with chest pain of presumed cardiac origin. Serum cTnT was determined in 132 patients and in 106 apparently healthy controls by both assays. The hs-cTnT outperformed the standard generation assay by: i) allowing a larger and earlier diagnosis of AMI (74.2 percent vs. 64.3 percent patients resulted positive at the final diagnosis of AMI when tested with the hs-cTnT or the std-cTnT assay, respectively); ii) showing a better time-dependent dynamics in patients with AMI due to a higher precision at low concentrations; iii) identifying, within the controls, 6 subjects in whom a further examination revealed the presence of chronic asymptomatic cardiac ischemia. The results underscore the excellent performance of the hs-cTnT assay in our population. The use of this test can thus be strongly recommended in subjects presenting to the emergency unit with chest pain of presumed ischemic origin in order to increase the probability of earlier diagnosis of AMI, especially in non-STEMI.
  Frontiers in bioscience (Elite edition) 01/2012; 4:2322-7.
• Article: MicroRNA-133 controls vascular smooth muscle cell phenotypic switch in vitro and vascular remodeling in vivo.

  Daniele Torella, Claudio Iaconetti, Daniele Catalucci, Georgina M Ellison, Angelo Leone, Cheryl D Waring, Angela Bochicchio, Carla Vicinanza, Iolanda Aquila, Antonio Curcio, Gianluigi Condorelli, Ciro Indolfi
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  ABSTRACT: MicroRNA (miR)-1 and -133 play a crucial role in skeletal and cardiac muscle biology and pathophysiology. However, their expression and regulation in vascular cell physiology and disease is currently unknown. The aim of the present study was to evaluate the role, if any, of miR-1 and miR-133 in vascular smooth muscle cell (VSMC) phenotypic switch in vitro and in vivo. We demonstrate here that miR-133 is robustly expressed in vascular smooth muscle cells (VSMCs) in vitro and in vivo, whereas miR-1 vascular levels are negligible. miR-133 has a potent inhibitory role on VSMC phenotypic switch in vitro and in vivo, whereas miR-1 does not have any relevant effect per se. miR-133 expression is regulated by extracellular signal-regulated kinase 1/2 activation and is inversely correlated with VSMC growth. Indeed, miR-133 decreases when VSMCs are primed to proliferate in vitro and following vascular injury in vivo, whereas it increases when VSMCs are coaxed back to quiescence in vitro and in vivo. miR-133 loss- and gain-of-function experiments show that miR-133 plays a mechanistic role in VSMC growth. Accordingly, adeno-miR-133 reduces but anti-miR-133 exacerbates VSMC proliferation and migration in vitro and in vivo. miR-133 specifically suppresses the transcription factor Sp-1 expression in vitro and in vivo and through Sp-1 repression regulates smooth muscle gene expression. Our data show that miR-133 is a key regulator of vascular smooth muscle cell phenotypic switch in vitro and in vivo, suggesting its potential therapeutic application for vascular diseases.
  Circulation Research 08/2011; 109(8):880-93. · 9.49 Impact Factor
• Source

  Available from: Armando Pérez de Prado

  Article: Endogenous cardiac stem cell activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary injection fosters survival and regeneration of the infarcted pig heart.

  Georgina M Ellison, Daniele Torella, Santo Dellegrottaglie, Claudia Perez-Martinez, Armando Perez de Prado, Carla Vicinanza, Saranya Purushothaman, Valentina Galuppo, Claudio Iaconetti, Cheryl D Waring, Andrew Smith, Michele Torella, Carlos Cuellas Ramon, Jose Manuel Gonzalo-Orden, Valter Agosti, Ciro Indolfi, Manuel Galiñanes, Felipe Fernandez-Vazquez, Bernardo Nadal-Ginard
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  ABSTRACT: The purpose of this study was to test the ability of insulin-like growth factor (IGF)-1/hepatocyte growth factor (HGF) to activate resident endogenous porcine cardiac stem/progenitor cells (epCSCs) and to promote myocardial repair through a clinically applicable intracoronary injection protocol in a pig model of myocardial infarction (MI) relevant to human disease. In rodents, cardiac stem/progenitor cell (CSC) transplantation as well as in situ activation through intramyocardial injection of specific growth factors has been shown to result in myocardial regeneration after acute myocardial infarction (AMI). Acute MI was induced in pigs by a 60-min percutaneous transluminal coronary angiography left anterior descending artery occlusion. The IGF-1 and HGF were co-administered through the infarct-related artery in a single dose (ranging from 0.5 to 2 μg HGF and 2 to 8 μg IGF-1) 30 min after coronary reperfusion. Pigs were sacrificed 21 days later for dose-response relationship evaluation by immunohistopathology or 2 months later for cardiac function evaluation by cardiac magnetic resonance imaging. The IGF-1/HGF activated c-kit positive-CD45 negative epCSCs and increased their myogenic differentiation in vitro. The IGF-1/HGF, in a dose-dependent manner, improved cardiomyocyte survival, and reduced fibrosis and cardiomyocyte reactive hypertrophy. It significantly increased c-kit positive-CD45 negative epCSC number and fostered the generation of new myocardium (myocytes and microvasculature) in infarcted and peri-infarct/border regions at 21 and 60 days after AMI. The IGF-1/HGF reduced infarct size and improved left ventricular function at 2 months after AMI. In an animal model of AMI relevant to the human disease, intracoronary administration of IGF-1/HGF is a practical and effective strategy to reduce pathological cardiac remodeling, induce myocardial regeneration, and improve ventricular function.
  Journal of the American College of Cardiology 06/2011; 58(9):977-86. · 14.16 Impact Factor
• Article: Mechanisms of smooth muscle cell proliferation and endothelial regeneration after vascular injury and stenting: approach to therapy.

  Antonio Curcio, Daniele Torella, Ciro Indolfi
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  ABSTRACT: Bare metal stents (BMS) successfully prevented abrupt artery closure and reduced the restenosis rate compared with balloon angioplasty. This review summarizes laboratory and recent clinical investigations concerning neointimal formation and endothelial regeneration after vascular injury. BMS efficacy was severely hampered by proliferating vascular smooth muscle cells (VSMCs), and the resultant neointimal hyperplasia, which is the only mechanism responsible for restenosis after metal stent placement. The advent of drug-eluting stents (DES) in 2002 have since then revolutionized interventional cardiology. By using the stent struts as a platform coated with polymers to elute drugs targeting VSMC proliferation, a substantial attenuation of in-stent restenosis is feasible. As with any medical innovation this technology still has restrictive factors, and novel approaches are promoted to improve the safety and efficacy of DES. Indeed, the antiproliferative properties of DES impair and/or delay endothelialization, hence leading to late stent thrombosis. Improvements in percutaneous coronary intervention procedures include the use of the so-called "second-generation DES", together with new coating technologies, bioabsorbable stents, and non-drug-based stent coatings. Particular emphasis will be placed on the concept that endothelial regeneration might be pursued as well as reduction of VSMC proliferation to allow stable successful revascularization after DES deployment.
  Circulation Journal 05/2011; 75(6):1287-96. · 3.77 Impact Factor
• Article: EGFR trans-activation by urotensin II receptor is mediated by β-arrestin recruitment and confers cardioprotection in pressure overload-induced cardiac hypertrophy.

  Giovanni Esposito, Cinzia Perrino, Alessandro Cannavo, Gabriele G Schiattarella, Francesco Borgia, Anna Sannino, Gianluigi Pironti, Giuseppe Gargiulo, Luigi Di Serafino, Anna Franzone, Laura Scudiero, Paolo Grieco, Ciro Indolfi, Massimo Chiariello
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  ABSTRACT: Urotensin II (UTII) and its seven trans-membrane receptor (UTR) are up-regulated in the heart under pathological conditions. Previous in vitro studies have shown that UTII trans-activates the epidermal growth factor receptor (EGFR), however, the role of such novel signalling pathway stimulated by UTII is currently unknown. In this study, we hypothesized that EGFR trans-activation by UTII might exert a protective effect in the overloaded heart. To test this hypothesis, we induced cardiac hypertrophy by transverse aortic constriction (TAC) in wild-type mice, and tested the effects of the UTII antagonist Urantide (UR) on cardiac function, structure, and EGFR trans-activation. After 7 days of pressure overload, UR treatment induced a rapid and significant impairment of cardiac function compared to vehicle. In UR-treated TAC mice, cardiac dysfunction was associated with reduced phosphorylation levels of the EGFR and extracellular-regulated kinase (ERK), increased apoptotic cell death and fibrosis. In vitro UTR stimulation induced membrane translocation of β-arrestin 1/2, EGFR phosphorylation/internalization, and ERK activation in HEK293 cells. Furthermore, UTII administration lowered apoptotic cell death induced by serum deprivation, as shown by reduced TUNEL/Annexin V staining and caspase 3 activation. Interestingly, UTII-mediated EGFR trans-activation could be prevented by UR treatment or knockdown of β-arrestin 1/2. Our data show, for the first time in vivo, a new UTR signalling pathway which is mediated by EGFR trans-activation, dependent by β-arrestin 1/2, promoting cell survival and cardioprotection.
  Archiv für Kreislaufforschung 03/2011; 106(4):577-89. · 7.35 Impact Factor
• Article: Mitogen-activated protein kinases activation in T lymphocytes of patients with acute coronary syndromes.

  Ciro Indolfi, Cosimo Gasparri, Carla Vicinanza, Daniela De Serio, Duino Boncompagni, Annalisa Mongiardo, Carmen Spaccarotella, Valter Agosti, Daniele Torella, Antonio Curcio
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  ABSTRACT: Current available biomarkers cannot identify myocardial ischemia without necrosis. To overcome this issue and to increase diagnostic power, we evaluated the activation of the three MAPK pathways, ERK1/2, JNK and p38, in T lymphocytes of patients with acute coronary syndromes (ACS). We included sixty consecutive patients affected by either unstable angina (UA, N = 22), Non- ST-segment elevation MI (NSTEMI, N = 19) or ST-segment elevation MI (STEMI, N = 19). Two separate groups of patients were matched as controls: healthy subjects (CTRL, N = 20) and patients with stable coronary artery disease (CAD, N = 21). MAPK activation in T lymphocytes, measured by phospho-ERK1/2, phospho-JNK and phospho-p38 levels, was assessed by flow cytometry analysis which revealed significantly increased phosphorylated levels of ERK1/2 in patients with UA, compared to controls. In UA patients no significant changes were detected for phospho-JNK compared to both control groups. NSTEMI and STEMI groups showed a statistically significant increase in both phospho-ERK1/2 and phospho-JNK, compared to control groups. All ACS groups demonstrated significantly increased phosphorylation of p38 compared to CTRL, but not CAD. ROC curves showed that a cut-off value of 22.5 intensity of fluorescence for phospho-ERK1/2 was able to significantly discriminate UA patients from patients with stable angina with 78% sensitivity and 90% specificity. Therefore, a differential MAPK activation in T lymphocytes denotes patients with ACS. Indeed, patients with unstable angina are identified with high specificity by activated ERK1/2 and normal JNK levels. These data could represent a valuable new molecular signature to be used as specific biomarkers for the diagnosis of unstable angina within ACS.
  Archiv für Kreislaufforschung 03/2011; 106(4):667-79. · 7.35 Impact Factor
• Article: Blocking out the real diagnosis.

  Antonio Gambardella, Antonio Curcio, Angelo Labate, Laura Mumoli, Ciro Indolfi, Aldo Quattrone
  The Lancet 02/2011; 377(9766):690. · 38.28 Impact Factor
• Article: OFFgel-based multidimensional LC-MS/MS approach to the cataloguing of the human platelet proteome for an interactomic profile.

  Shibu Krishnan, Marco Gaspari, Anna Della Corte, Patrizia Bianchi, Marilena Crescente, Chiara Cerletti, Daniele Torella, Ciro Indolfi, Giovanni de Gaetano, Maria Benedetta Donati, Domenico Rotilio, Giovanni Cuda
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  ABSTRACT: The proteome of quiescent human platelets was analyzed by a shotgun proteomics approach consisting of enzymatic digestion, peptide separation based on isoelectric point by the use of OFFgel fractionation and, finally, RP nanoscale chromatography coupled to MS/MS detection (nano-LC-MS/MS). OFFgel fractionation in the first dimension was effective in providing an additional dimension of separation, orthogonal to RP nano-LC, thus generating an off-line multidimensional separation platform that proved to be robust and easy to set up. The analysis identified 1373 proteins with high confidence (false discovery rate<0.25%). The core set of 1373 human platelet proteins was investigated by Ingenuity Pathway Analysis software from which ten canonical pathways and eight networks have been validated, to suggest that platelets behave either as inflammatory or immune cells, and plasma membrane and cytoskeleton proteins play a fundamental role in their function. Moreover, toxicity pathway in agreement with network analysis, supports the concept that platelet life span is governed by an apoptotic mechanism.
  Electrophoresis 02/2011; 32(6-7):686-95. · 3.30 Impact Factor
• Source

  Available from: Michele D'Alto

  Article: Aortic and left ventricular remodeling in patients with bicuspid aortic valve without significant valvular dysfunction: a prospective study.

  Giuseppe Santarpia, Giancarlo Scognamiglio, Giovanni Di Salvo, Michele D'Alto, Berardo Sarubbi, Emanuele Romeo, Ciro Indolfi, Maurizio Cotrufo, Raffaele Calabrò
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  ABSTRACT: Bicuspid aortic valve (BAV) represents the most common cardiac congenital malformation in the adult age. It is frequently associated with dilatation, aneurysm and dissection of the ascending aorta. The purpose of the following study was to evaluate in patients with BAV: 1) the elastic properties of the ascending aorta, 2) the mechanical function of the left ventricle and 3) stiffness, elasticity and strain of the epi-aortic vessels wall. Forty BAV patients (28M/12F; age 20.9 ± 4.7 years; range 17-26) with no or mild valvular impairment were recruited with 40 control subjects (25M/15F; age 23.4 ± 3.4 years; range 15-31) matched for age, gender and body surface area (BSA). Aortic strain, aortic distensibility (AoDIS) and aortic stiffness index (AoSI) were derived. Left ventricular strain was acquired. Elastic properties of epi-aortic vessels were evaluated. BAVs vs. controls had increased systolic and diastolic aortic diameters (p<0.001). Aortic strain (%) was lower in BAVs than in controls (8.3 ± 3.6 vs. 11.2 ± 2.6; p<0.001) as well as AoDIS (10(-6)cm(2)dyn(-1)) (6.5 ± 2.8 vs. 8.8 ± 2.9; p=0.002), while AoSI was greater in BAVs (6.4 ± 3.5 vs. 3.9 ± 1.2; p<0.001). Both AoDIS and aortic strain were related to aortic size in BAVs and controls. Left ventricular longitudinal (p=0.01), circumferential (p=0.01) and radial (p<0.001) strain (%) were lower in BAVs. No significant differences were found in elastic properties of epi-aortic vessels. Bicuspid aortic valve is associated with an increased aortic stiffness and with a reduction of the aortic and left ventricular deformation properties. Epi-aortic vessels do not seem to be interested by the disease. The use of an echocardiographic method that can estimate the degree of aortic and left ventricular remodeling can provide great benefits in the selection of patients with BAV to be treated and in determining the time for beginning drug therapy.
  International journal of cardiology 02/2011; 158(3):347-52. · 7.08 Impact Factor
• Article: AKAP121 downregulation impairs protective cAMP signals, promotes mitochondrial dysfunction, and increases oxidative stress.

  Cinzia Perrino, Antonio Feliciello, Gabriele G Schiattarella, Giovanni Esposito, Rosalia Guerriero, Laura Zaccaro, Annarita Del Gatto, Michele Saviano, Corrado Garbi, Rosa Carangi, Emilio Di Lorenzo, Giuseppe Donato, Ciro Indolfi, Vittorio Enrico Avvedimento, Massimo Chiariello
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  ABSTRACT: The aim of the present study was to determine the function and the role of the scaffold protein AKAP121, tethering cAMP dependent protein kinase A to the outer wall of mitochondria, in neonatal ventricular myocytes and the heart. Competitive peptides displacing AKAP121 from mitochondria in the tissue and in the cells were used to investigate the role of AKAP121 in mitochondrial function, reactive oxygen species (ROS) generation, and cell survival. Displacement of AKAP121 from mitochondria by synthetic peptides triggers the death program in cardiomyocytes. Under pathological conditions in vivo, in a rat model of cardiac hypertrophy induced by ascending aorta banding, the levels of AKAP121 are significantly down-regulated. Disappearance of AKAP121 is associated with mitochondrial dysfunction, high oxidative stress, and apoptosis. In vivo delocalization of AKAP121 by competitive peptides replicates some of the molecular signatures induced by pressure overload: mitochondrial dysfunction, increased mitochondrial ROS, and apoptosis. These data suggest that AKAP121 regulates the response to stress in cardiomyocytes, and therefore AKAP121 downregulation might represent an important event contributing to the development of cardiac dysfunction.
  Cardiovascular research 10/2010; 88(1):101-10. · 5.80 Impact Factor
• Article: Mediterranean jellyfish sting-induced Tako-Tsubo cardiomyopathy.

  Renatomaria Bianchi, Daniele Torella, Carmen Spaccarotella, Annalisa Mongiardo, Ciro Indolfi
  European Heart Journal 09/2010; 32(1):18. · 10.48 Impact Factor
• Source

  Available from: Cristiano Amarelli

  Article: LOWERing the INtensity of oral anticoaGulant Therapy in patients with bileaflet mechanical aortic valve replacement: results from the "LOWERING-IT" Trial.

  Michele Torella, Daniele Torella, Paolo Chiodini, Marco Franciulli, Giampaolo Romano, Luca De Santo, Marisa De Feo, Cristiano Amarelli, Ferdinando C Sasso, Teresa Salvatore, Georgina M Ellison, Ciro Indolfi, Maurizio Cotrufo, Gianantonio Nappi
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  ABSTRACT: Moderate anticoagulation after mechanical heart valve replacement has been proposed to reduce the risk of bleeding related to lifelong anticoagulation. However, the efficacy of such reduced antithrombotic regimens is still unknown. The present prospective open-label, single-center, randomized controlled trial aimed to evaluate the safety and feasibility of reduced oral anticoagulation after isolated mechanical aortic valve replacement. Low-risk patients undergoing bileaflet mechanical aortic valve replacement were randomized to a low International normalized ratio (INR) target (1.5-2.5; LOW-INR group) or to the standard currently recommended INR (2.0-3.0; CONVENTIONAL-INR group) through daily coumarine oral therapy. No aspirin was added. Median follow-up was 5.6 years. The primary outcome was assessment of noninferiority of the low over the standard anticoagulation regimen on thromboembolic events. Secondary end point was the superiority of the reduced INR target strategy on bleeding events. We analyzed 396 patients (197 in the LOW-INR group and 199 in the CONVENTIONAL-INR group). The mean of INR was 1.94 +/- 0.21 and 2.61 +/- 0.25 in the LOW-INR and CONVENTIONAL-INR groups, respectively (P < .001). One versus three thromboembolic events occurred in the LOW-INR and CONVENTIONAL-INR, respectively, meeting the noninferiority criterion (P = .62). Total hemorrhagic events occurred in 6 patients in the LOW-INR group and in 16 patients in the CONVENTIONAL-INR group (P = .04). LOWERING-IT trial established that the proposed LOW-INR target is safe and feasible in low-risk patients after bileaflet aortic mechanical valve replacement. It results in similar thrombotic events and in a significant reduction of bleeding occurrence when compared to the conventional anticoagulation regimen.
  American heart journal 07/2010; 160(1):171-8. · 4.65 Impact Factor
• Article: A clinical and angiographic study of the XIENCE V everolimus-eluting coronary stent system in the treatment of patients with multivessel coronary artery disease. Study design and rationale of the EXECUTIVE trial.

  Flavio Ribichini, Gerardo Ansalone, Antonio Bartorelli, Federico Beqaraj, Andrea Berni, Salvatore Colangelo, Maurizio D'Amico, Francesco Della Rovere, Antonio Fiscella, Gabriele Gabrielli, [......], Diego Milazzo, Michele Romano, Pietro Sangiorgio, Imad Sheiban, Corrado Tamburino, Bernardino Tuccillo, Rosvaldo Villani, Barbara Cappi, Maria Josè Lopera Quijada, Corrado Vassanelli
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  ABSTRACT: Myocardial revascularization with drug-eluting stents (DESs) is emerging as an alternative to conventional coronary artery bypass surgery in patients with multivessel coronary artery disease (MV-CAD). First-generation DESs have yielded equivalent safety results at mid-term compared with surgery, but inferior efficacy in preventing the recurrence of ischemic symptoms. The outcome of percutaneous coronary intervention with a second-generation everolimus DES as compared with a paclitaxel DES in patients with MV-CAD has not been established. The aim of the study is the assessment of the efficacy and performance of the XIENCE V everolimus-eluting stent in the treatment of de-novo coronary artery lesions in patients with MV-CAD. The study is composed of two parts: a prospective, double arm, randomized multicenter trial to assess the angiographic efficacy of the XIENCE V everolimus-eluting coronary stent system (EECSS) compared with the Taxus Liberté Paclitaxel Eluting Coronary Stent System (Taxus Liberté Stent) and a prospective, open-label, single arm, controlled registry to analyze the clinical efficacy and safety of XIENCE V EECSS at mid-term and long-term follow-up in patients treated for MV-CAD. For the EXECUTIVE randomized trial, the primary endpoint is in-stent late lumen loss at 9 months. For the EXECUTIVE registry, the primary endpoint is a composite of all death, myocardial infarction (Q-wave and non-Q-wave), and ischemia-driven target vessel revascularization at 12 months. The study will be conducted at 30 study centers in Italy and 600 patients will be enrolled in total: 200 patients will be enrolled (1: 1) in the randomized trial and 400 patients will enter the registry. It was calculated that, assuming a mean in-stent late lumen loss of 0.20 +/- 0.41 mm in the XIENCE V EECSS arm and 0.30 +/- 0.53 mm in the Taxus Liberté stent arm, and a noninferiority margin delta of 0.12 (according to the SPIRIT III results), the analysis of 81 lesions per arm would provide over 90% power. Therefore, 200 patients will be enrolled to account for dropouts. The present study is expected to provide as yet unavailable information about the performance of second-generation stents in the specific setting of patients with MV-CAD.
  Journal of Cardiovascular Medicine 04/2010; 11(4):299-309. · 1.51 Impact Factor
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  Available from: PubMed Central

  Article: Outcome of open and endovascular repair in acute type B aortic dissection: a retrospective and observational study.

  Pasquale Mastroroberto, Francesco Onorati, Saverio Zofrea, Attilio Renzulli, Ciro Indolfi
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  ABSTRACT: The aim of the study was to analyze surgical and endovascular results in the treatment of acute type B aortic dissection (B AAD). Retrospective and observational analysis with patient inclusion between January 2001-December 2008 and follow-up ranged from 2 to 96 months (median = 47.2) was performed. Out of 51 consecutive patients with B AAD, 11 (21.6%) had to undergo open surgery (OS) and 13 (25.5%) endovascular treatment (TEVAR). There was a significantly difference in early mortality in the TEVAR group (0/13,0%) vs OS group (4/11,36.4%, P < 0.05) and in the incidence of paraplegia/paraparesis (OS 2,28.6% vs TEVAR 1,7.7%, P < 0.05), renal failure (OS 3, 42.8% vs TEVAR 1, 7.7%, P < 0.05), respiratory failure (OS 2,28.6% vs TEVAR 1,7.7%, P < 0.05) and cerebrovascular accident (OS 1,14.3% vs TEVAR 0,0%, P < 0.05). The late mortality at a follow-up was 30.8% (4/13) in the TEVAR group and 42.8% (3/7) in the OS group, respectively (P = not significant). The cumulative survival rate after 1, 3 and 8 years was 93%, 84%, and 69% in the TEVAR group and 86%, 71% and 57% in the OS group, respectively. Endoleaks were diagnosed in 2/13 endovascular patients (15.4%). TEVAR group had a significantly reduction in early mortality and postoperative complications. No significant differences were found in terms of cumulative survival at follow-up. On this basis TEVAR could be considered an option in the treatment of these complex cases with all proper reservation especially related to the small sample sizes examined.
  Journal of Cardiothoracic Surgery 04/2010; 5:23. · 1.19 Impact Factor
• Article: Proteomics reveals high levels of vitamin D binding protein in myocardial infarction.

  Cosimo Gasparri, Antonio Curcio, Daniele Torella, Marco Gaspari, Vittoria Celi, Francesco Salituri, Duino Boncompagni, Michele Torella, Elio Gulletta, Giovanni Cuda, Ciro Indolfi
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  ABSTRACT: The pathogenic mechanisms underlying cardiovascular diseases involve significant alterations in myocardial gene and protein expression. Proteomics analysis can define new protein and peptide changes associated with cardiac pathology, including myocardial infarction. The aim of the present study was to analyze serum proteome of patients with ST-Elevation myocardial infarction (STEMI). Serum samples were collected from STEMI patients (age 65.0+/-10.3) at 5.3+/-2.7 hours after the onset of typical chest pain and before initiating standard therapy. Ten age- and sex-matched donors were used as controls. The samples were albumin- and IgG-depleted. Isotope-coded affinity tag method was employed to label cysteine residues and liquid chromatography-Tandem Mass Spectrometry analysis was performed to measure the labeled proteins. Our proteomic approach identified increased levels of vitamin D-binding protein precursor (VDB) in the serum of STEMI patients when compared to control donors. Western blot analysis confirmed the increase in VDB protein in STEMI patients. Moreover, fresh thrombotic plaques, obtained during primary angioplasty, showed high expression of VDB protein. Mechanistically, VDB protein reduces platelet aggregation and prolongs coagulation time ex vivo.
  Frontiers in bioscience (Elite edition) 01/2010; 2:796-804.