Marco Proietti

Publications (4)14.72 Total impact

• Article: Role of platelets in NOX2 activation mediated by TNFα in heart failure.

  Roberto Cangemi, Andrea Celestini, Maria Del Ben, Pasquale Pignatelli, Roberto Carnevale, Marco Proietti, Cinzia Myriam Calabrese, Stefania Basili, Francesco Violi
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  ABSTRACT: Tumor necrosis factor (TNF) α may contribute to the deterioration of cardiovascular function in heart failure (HF) through various mechanisms, including the generation of reactive oxygen species (ROS). NADPH oxidase is the major source of ROS in the vascular system, but the interplay between TNFα and NADPH oxidase activation is elusive. As platelets possess NADPH oxidase enzyme, they represent an important tool to investigate the interplay between NADPH oxidase and TNFα in patients with HF. Serum gp91phox (NOX2), the catalytic core of NADPH oxidase, and serum TNFα were measured in 120 HF patients and in 60 healthy subjects. Compared with healthy subjects, HF patients had higher blood levels of NOX2 and TNFα with a progressive increase from NYHA I to NYHA IV classes. NOX2 levels in blood were independently associated with TNFα in HF patients. An in vitro study, performed on platelets from a subgroup of HF patients, shows that TNFα, at concentrations commonly found in HF patients' peripheral circulation, activates platelet NOX2. Thus, TNFα increases ROS production and the extracellular levels of NOX2. These phenomena are inhibited by the NOX2-specific blocking peptide gp91ds-tat. The study provides evidence that circulating NOX2, as well as the activation of NOX2 on platelets, is increased in HF likely as a consequence of the underlying inflammatory process.
  Internal and Emergency Medicine 07/2012; · 2.06 Impact Factor
• Source

  Available from: Francesco Angelico

  Article: Platelet isoprostane overproduction in diabetic patients treated with aspirin.

  Roberto Cangemi, Pasquale Pignatelli, Roberto Carnevale, Carmen Nigro, Marco Proietti, Francesco Angelico, Davide Lauro, Stefania Basili, Francesco Violi
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  ABSTRACT: Aspirin modestly influences cardiovascular events in patients with type 2 diabetes mellitus (T2DM), but the reason is unclear. The aim of the study was to determine whether in T2DM patients aspirin enhances platelet isoprostanes, which are eicosanoids with proaggregating properties derived from arachidonic acid oxidation by platelet NOX2, the catalytic subunit of reduced NAD phosphate oxidase. A cross-sectional study was performed comparing T2DM patients, treated (n = 50) or not treated (n = 50) with 100 mg/day aspirin, with 100 nondiabetic patients, matched for age, sex, atherosclerosis risk factors, and aspirin treatment. A short-term (7 days) treatment with 100 mg/day aspirin also was performed in 36 aspirin-free diabetic and nondiabetic patients. Higher platelet recruitment, platelet isoprostane, and NOX2 activation was found in diabetic versus nondiabetic patients and in aspirin-treated diabetic patients versus nontreated patients (P < 0.001). Platelet thromboxane (Tx) A(2) (P < 0.001) was inhibited in all aspirin-treated patients. In the interventional study, aspirin similarly inhibited platelet TxA(2) in diabetic and nondiabetic patients (P < 0.001). Platelet recruitment, isoprostane levels, and NOX2 activation showed a parallel increase in diabetic patients (P < 0.001) and no changes in nondiabetic patients. These findings suggest that in aspirin-treated diabetic patients, oxidative stress-mediated platelet isoprostane overproduction is associated with enhanced platelet recruitment, an effect that mitigates aspirin-mediated TxA(2) inhibition.
  Diabetes 03/2012; 61(6):1626-32. · 8.29 Impact Factor
• Article: Ascorbic acid infusion blunts CD40L upregulation in patients undergoing coronary stent.

  Pasquale Pignatelli, Gaetano Tanzilli, Roberto Carnevale, Serena Di Santo, Lorenzo Loffredo, Andrea Celestini, Marco Proietti, Priscilla Tovaglia, Enrico Mangieri, Stefania Basili, Francesco Violi
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  ABSTRACT: To reduce the increase of oxidative stress and the upregulation of CD40L during stenting procedure using ascorbic acid infusion. Background: CD40L upregulation occurring after coronary percutaneous coronary intervention predicts vascular events but the underlying mechanism is still unclear. Fifty-six patients undergoing elective coronary stenting were randomly allocated to intravenous infusion of the antioxidant ascorbic acid or placebo. Platelet CD40L and plasma levels of soluble CD40L and of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress, were measured before and after coronary stenting. In vitro study was also done to measure reactive oxidant species and CD40L expression in platelets exposed to anoxia-reoxygenation. Placebo-treated patients showed a significant increase of platelet CD40L, soluble CD40L and 8-hydroxy-2'-deoxyguanosine compared to baseline values. Patients given ascorbic acid showed no change of soluble CD40L and platelet CD40L but a significant decrease of 8-hydroxy-2'-deoxyguanosine. After 60 and 120 min, soluble CD40L, platelet CD40L and 8-hydroxy-2'-deoxyguanosine were significantly lower in the ascorbic acid-treated group compared to the placebo-treated one. A significant correlation between platelet CD40L and soluble CD40L and between soluble CD40L and 8-hydroxy-2'-deoxyguanosine was observed. Platelets, in vitro exposed to anoxia-reoxygenation, had a burst of ROS and an upregulation of CD40L that were inhibited by ascorbic acid or apocynin, an inhibitor of NADPH oxidase. This study shows that in patients undergoing coronary stenting CD40L is upregulated with a mechanism which is likely mediated by oxidative stress.
  Cardiovascular Therapeutics 12/2011; 29(6):385-94. · 2.35 Impact Factor
• Article: VEGF-A gene promoter polymorphisms and microvascular complications in patients with essential hypertension.

  Raffaele Palmirotta, Patrizia Ferroni, Giorgia Ludovici, Francesca Martini, Annalisa Savonarola, Roberta D'Alessandro, Valeria Raparelli, Marco Proietti, Antongiulio Scarno, Silvia Riondino, Stefania Basili, Fiorella Guadagni
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  ABSTRACT: We investigated the possible involvement of vascular endothelial growth factor (VEGF-A) gene promoter polymorphisms in essential hypertension (EH). 1225bp of the VEGF-A gene promoter were screened for polymorphisms using PCR amplification and direct DNA sequence analysis in 62 EH and 62 normotensive (HS) individuals. Circulating VEGF-A levels were determined by immunoassay. -152G/A (p=0.009) and -116G/A (p=0.016) polymorphisms were correlated to hypertension (p<0.05). Median platelet VEGF-A load in EH was 2.10fg/plt. Patients with microvascular complications (MC) had higher platelet VEGF-A load than those without (p=0.005). Multivariate analyses showed that -116 A allele was an independent predictor of microalbuminuria (p=0.014) and increased platelet VEGF-A load (p=0.009) in EH. Platelet VEGF-A load independently predicted MC (p=0.049) in addition to -116G/A polymorphism (p=0.035). Abnormal regulation of VEGF-A due to polymorphism at position -116 might represent a genetic factor for increased VEGF-A production and MC in EH.
  Clinical biochemistry 09/2010; 43(13-14):1090-5. · 2.02 Impact Factor