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Article ; Online: Cellular Strategies for Separating GvHD from GvL in Haploidentical Transplantation.

Di Ianni, Mauro / Liberatore, Carmine / Santoro, Nicole / Ranalli, Paola / Guardalupi, Francesco / Corradi, Giulia / Villanova, Ida / Di Francesco, Barbara / Lattanzio, Stefano / Passeri, Cecilia / Lanuti, Paola / Accorsi, Patrizia

Cells

2024 Volume 13, Issue 2

Abstract: GvHD still remains, despite the continuous improvement of transplantation platforms, a fearful complication of transplantation from allogeneic donors. Being able to separate GvHD from GvL represents the greatest challenge in the allogeneic transplant ... ...

Abstract	GvHD still remains, despite the continuous improvement of transplantation platforms, a fearful complication of transplantation from allogeneic donors. Being able to separate GvHD from GvL represents the greatest challenge in the allogeneic transplant setting. This may be possible through continuous improvement of cell therapy techniques. In this review, current cell therapies are taken into consideration, which are based on the use of TCR alpha/beta depletion, CD45RA depletion, T regulatory cell enrichment, NK-cell-based immunotherapies, and suicide gene therapies in order to prevent GvHD and maximally amplify the GvL effect in the setting of haploidentical transplantation.
MeSH term(s)	Humans ; Transplantation, Haploidentical ; Cell- and Tissue-Based Therapy ; Fear ; Immunotherapy ; Killer Cells, Natural
Language	English
Publishing date	2024-01-11
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13020134
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Article ; Online: Study of pulsed electrostatic field (PESF) in the perfusion of peripheral tissues: Microangiopathy, nutrition and quality of perceiver life.

Liani, Rossella / La Torre, Sara / Liani, Valentina / Melchiorre, Angela / D'Ettorre, Danilo / Tripaldi, Romina / Lattanzio, Stefano / Di Luzio, Rossano / Coli, Mauro / Velussi, Carlo

PloS one

2022 Volume 17, Issue 9, Page(s) e0268497

Abstract: Microangiopathy compromises the structural and functional integrity of organs and tissues in patients with type II diabetes mellitus (T2DM) negatively affecting the perceived quality of life. Nitric oxide (NO) is a multifunctional signalling molecule, ... ...

Abstract	Microangiopathy compromises the structural and functional integrity of organs and tissues in patients with type II diabetes mellitus (T2DM) negatively affecting the perceived quality of life. Nitric oxide (NO) is a multifunctional signalling molecule, acting as a vasodilator, neurotransmitter, and modulator of inflammatory processes. Patients with type II diabetes mellitus and chronic kidney disease, controlled from glycaemic status, were treated or not with pulsed electrostatic field (PESF) cycles to evaluate effect on the perfusion of peripheral tissues. Everyone was monitored for the metabolic profile, and we tested circulating NO with a commercial enzyme immunoassay kit. In addition, we tested the perceived quality of life of patients before/after a PESF cycle using a questionnaire. Patients treated with PESF were improved circulating NO levels, significant changes in systolic and diastolic blood pressure, heart rate and were more homogeneous for their metabolic profile. The questionnaire showed also a marked improvement in the perceived quality of life. The use of pulsed electrostatic fields has allowed us to observe an improvement in the metabolic, psychological, and clinical profile in patients with T2DM and chronic kidney disease whose pathological profile is strongly compromised.
MeSH term(s)	Diabetes Mellitus, Type 2 ; Humans ; Nitric Oxide ; Perfusion ; Quality of Life ; Renal Insufficiency, Chronic/therapy ; Static Electricity ; Vascular Diseases ; Vasodilator Agents
Chemical Substances	Vasodilator Agents ; Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2022-09-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0268497
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Article ; Online: Ultrarush venom immunotherapy and the lipoxin a4 inflammation resolution pathway.

Gangemi, Sebastiano / Patella, Vincenzo / Cianci, Eleonora / Saitta, Salvatore / Lattanzio, Stefano / Florio, Giovanni / Romano, Mario

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology

2012 Volume 109, Issue 3, Page(s) 226–227

MeSH term(s)	Adult ; Animals ; Arthropod Venoms/administration & dosage ; Arthropod Venoms/immunology ; Bee Venoms/administration & dosage ; Bee Venoms/immunology ; Desensitization, Immunologic/adverse effects ; Desensitization, Immunologic/methods ; Female ; Humans ; Hymenoptera/immunology ; Hypersensitivity, Immediate/drug therapy ; Inflammation/etiology ; Inflammation/immunology ; Lipoxins/immunology ; Lipoxins/urine ; Male ; Middle Aged
Chemical Substances	Arthropod Venoms ; Bee Venoms ; Lipoxins ; lipoxin A4
Language	English
Publishing date	2012-09
Publishing country	United States
Document type	Letter
ZDB-ID	1228189-x
ISSN	1534-4436 ; 0003-4738 ; 1081-1206
ISSN (online)	1534-4436
ISSN	0003-4738 ; 1081-1206
DOI	10.1016/j.anai.2012.07.013
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Article ; Online: Pentraxin 3 and Platelet Activation in Obese Patients After Gastric Banding.

Santilli, Francesca / Guagnano, Maria Teresa / Innocenti, Paolo / Aceto, Liberato / Vazzana, Natale / Lattanzio, Stefano / Liani, Rossella / Tripaldi, Romina / Creato, Valeria / Romano, Mario / Davì, Giovanni

Circulation journal : official journal of the Japanese Circulation Society

2016 Volume 80, Issue 2, Page(s) 502–511

Abstract: Background: Circulating pentraxin 3 (PTX3), the main regulator of the inflammatory response, rapidly increases following cardiovascular events, and low PTX3 is associated with high body mass index.: Methods and results: We conducted a 12-month ... ...

Abstract	Background: Circulating pentraxin 3 (PTX3), the main regulator of the inflammatory response, rapidly increases following cardiovascular events, and low PTX3 is associated with high body mass index. Methods and results: We conducted a 12-month longitudinal study, to test the hypothesis that laparoscopic adjustable gastric banding (LAGB)-induced weight loss was associated with changes in platelet activation markers and PTX3. Twelve obese patients, scheduled to undergo LAGB, were enrolled at the University Obesity Center. Urinary 11-dehydro-thromboxane (Tx)B2excretion rate was measured on radioimmunoassay, and PTX3 and CD40L were determined on immunoassay. Plasma PTX3 increased by 178.8 and 214.9% (P<0.0001), respectively, 6 and 12 months after LAGB. High-sensitivity CRP decreased by 24 and 29.7% (P<0.0001), whereas CD40L decreased by 64.3 and 58.6% (P=0.002), respectively. Urinary 11-dehydro-TxB2decreased from 1,443 to 715 and 564 pg/mg creatinine, respectively 6 months and 12 months after LAGB (P<0.0001). PTX3 was inversely related to platelet activation markers, 11-dehydro-TxB2and CD40L. Moreover, multiple regression analysis on pooled data showed that plasma PTX3 was an independent predictor of urinary 11-dehydro-TxB2. Conclusions: There is an association between inflammation, platelet activation and metabolic dysfunction in obesity, and PTX3 is a key player within these circuits.
MeSH term(s)	Adult ; C-Reactive Protein/metabolism ; CD40 Ligand/blood ; Female ; Follow-Up Studies ; Gastric Bypass ; Humans ; Male ; Middle Aged ; Obesity/blood ; Obesity/surgery ; Obesity/urine ; Platelet Activation ; Serum Amyloid P-Component/metabolism ; Thromboxane B2/analogs & derivatives ; Thromboxane B2/urine
Chemical Substances	Serum Amyloid P-Component ; CD40 Ligand (147205-72-9) ; PTX3 protein (148591-49-5) ; Thromboxane B2 (54397-85-2) ; 11-dehydro-thromboxane B2 (67910-12-7) ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2016
Publishing country	Japan
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2068090-9
ISSN	1347-4820 ; 1346-9843
ISSN (online)	1347-4820
ISSN	1346-9843
DOI	10.1253/circj.CJ-15-0721
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Article ; Online: Determinants of thromboxane biosynthesis in patients with moderate to severe chronic kidney disease.

Vazzana, Natale / Santilli, Francesca / Lattanzio, Stefano / Liani, Mario / Giacci, Luciano / Del Rosso, Goffredo / Salvati, Filippo / Boccatonda, Andrea / Ferroni, Patrizia / Davì, Giovanni

European journal of internal medicine

2016 Volume 33, Page(s) 74–80

Abstract: Background: Mechanisms of accelerated atherothrombosis in patients with chronic kidney disease (CKD) are only partly characterized. The aims of this study were to evaluate the extent of thromboxane (TX)-dependent platelet activation in patients with CKD, ...

Abstract	Background: Mechanisms of accelerated atherothrombosis in patients with chronic kidney disease (CKD) are only partly characterized. The aims of this study were to evaluate the extent of thromboxane (TX)-dependent platelet activation in patients with CKD, and to characterize the determinants of altered TX biosynthesis in this setting, with particular reference to enhanced lipid peroxidation, low grade inflammation and CKD-related anemia. Patients and methods: A cross sectional comparison between urinary 8-iso-PGF2α and 11-dehydro-TXB2, in vivo markers of oxidative stress and platelet activation, respectively, was performed in 115 patients with stage 1-4 CKD. Results: Levels of both urinary 11-dehydro-TXB2 and 8-iso-PGF2α increased sequentially across the four CKD stages (P<0.0001, Kruskal-Wallis test). Both urinary prostanoids were inversely associated with either estimated glomerular filtration rate (eGFR, P<0.0001) or hemoglobin levels (P<0.0001). A significant direct correlation was also observed between urinary 11-dehydro-TXB2 and 8-iso-PGF2α (Rho=0.620, P<0.0001). On multivariate analysis, urinary 8-iso-PGF2α (β=0.459, P<0.0001), hemoglobin levels (β=- 0.261, P=0.002) and eGFR (β=-0.172, P=0.032) were independent predictors of urinary 11-dehydro-TXB2 (adjusted R(2)=0.488). Conclusions: This study provides biochemical evidence of persistent platelet activation in patients with CKD. This condition occurs early in the natural history of the disease and is related to kidney function and oxidative stress. Moreover, we found an independent inverse relationship between hemoglobin levels and TX-dependent platelet activation. This finding may provide a mechanistic link between CKD-related anemia and increased cardiovascular risk.
MeSH term(s)	Aged ; Biomarkers/urine ; Cardiovascular Diseases/epidemiology ; Cross-Sectional Studies ; Dinoprost/analogs & derivatives ; Dinoprost/urine ; Erythropoietin/blood ; Female ; Glomerular Filtration Rate ; Hemoglobins/analysis ; Humans ; Italy ; Linear Models ; Male ; Middle Aged ; Multivariate Analysis ; Oxidative Stress ; Platelet Activation ; Prostaglandins/biosynthesis ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/urine ; Risk Assessment ; Risk Factors ; Thromboxane B2/analogs & derivatives ; Thromboxane B2/urine
Chemical Substances	Biomarkers ; Hemoglobins ; Prostaglandins ; Erythropoietin (11096-26-7) ; 8-epi-prostaglandin F2alpha (27415-26-5) ; Thromboxane B2 (54397-85-2) ; 11-dehydro-thromboxane B2 (67910-12-7) ; Dinoprost (B7IN85G1HY)
Language	English
Publishing date	2016-09
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article
ZDB-ID	1038679-8
ISSN	1879-0828 ; 0953-6205
ISSN (online)	1879-0828
ISSN	0953-6205
DOI	10.1016/j.ejim.2016.06.016
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Article ; Online: Endogenous secretory RAGE in obese women: association with platelet activation and oxidative stress.

Vazzana, Natale / Guagnano, Maria Teresa / Cuccurullo, Chiara / Ferrante, Elisabetta / Lattanzio, Stefano / Liani, Rossella / Romano, Mario / Davì, Giovanni

The Journal of clinical endocrinology and metabolism

2012 Volume 97, Issue 9, Page(s) E1726–30

Abstract: Context: The receptor for advanced glycation end-products (RAGE) has been implicated in obesity-related metabolic disease and accelerated atherothrombosis.: Objective: We tested the hypothesis that changes in endogenous secretory (es)RAGE levels as a ...

Abstract	Context: The receptor for advanced glycation end-products (RAGE) has been implicated in obesity-related metabolic disease and accelerated atherothrombosis. Objective: We tested the hypothesis that changes in endogenous secretory (es)RAGE levels as a result of excess adiposity and oxidative stress may contribute to enhancing platelet activation in obese women, thus increasing the cardiovascular risk. Patients: Eighty otherwise healthy obese women and 20 nonobese women were studied. Results: esRAGE and plasma adiponectin were reduced in obese women [median (interquartile range), 0.18 (0.13-0.26) vs. 0.38 (0.20-0.48) ng/ml, P = 0.003; and 4.4 (2.8-6.4) vs. 10.0 (6.9-12.5) μg/ml, P < 0.0001, respectively] who also displayed higher urinary 11-dehydro-thromboxane B(2) (11-dehydro-TXB(2)) [795 (572-1089) vs. 211 (135-301) pg/mg creatinine; P < 0.0001] and 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)) [544 (402-698) vs. 149 (98-219) pg/mg creatinine; P < 0.0001] compared to nonobese women. Direct correlations between plasma adiponectin and esRAGE (Rho = 0.43; P < 0.0001) and between urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2) (Rho = 0.36; P = 0.001) were observed in obese women. Moreover, plasma esRAGE and urinary 11-dehdro-TXB(2) were inversely related (Rho = -0.29; P = 0.008). On multiple linear regression analysis, urinary 8-iso-PGF(2α) and plasma esRAGE were independent predictors of urinary 11-dehydro-TXB(2). In five obese women, a short-term weight loss program gave a significant increase in esRAGE and decrease in urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2). Conclusion: In otherwise healthy obese women, low plasma esRAGE levels are associated with reduced circulating adiponectin and enhanced thromboxane biosynthesis, which is in part mediated by increased lipid peroxidation. Thus, excess adiposity may be implicated in RAGE hyperactivation and thromboxane-dependent platelet activation, contributing to obesity-related metabolic and vascular disease.
MeSH term(s)	Adiponectin/blood ; Adult ; Anthropometry ; Blood Glucose/metabolism ; Blood Pressure/physiology ; Cardiovascular Diseases/epidemiology ; Dinoprost/analogs & derivatives ; Dinoprost/urine ; Female ; Humans ; Linear Models ; Lipid Peroxidation/physiology ; Lipids/blood ; Middle Aged ; Obesity/blood ; Obesity/metabolism ; Oxidative Stress/physiology ; Platelet Activation/physiology ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic/blood ; Receptors, Immunologic/metabolism ; Risk ; Thromboxane B2/analogs & derivatives ; Thromboxane B2/urine ; Weight Loss/physiology
Chemical Substances	Adiponectin ; Blood Glucose ; Lipids ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; 8-epi-prostaglandin F2alpha (27415-26-5) ; Thromboxane B2 (54397-85-2) ; 11-dehydro-thromboxane B2 (67910-12-7) ; Dinoprost (B7IN85G1HY)
Language	English
Publishing date	2012-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/jc.2012-1473
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Article: Oxidative stress and platelet activation in subjects with moderate hyperhomocysteinaemia due to MTHFR 677 C→T polymorphism.

Dragani, Alfredo / Falco, Angela / Santilli, Francesca / Basili, Stefania / Rolandi, Giancarlo / Cerasa, Loredana / Lattanzio, Stefano / Ciabattoni, Giovanni / Patrono, Carlo / Davì, Giovanni

Thrombosis and haemostasis

2012 Volume 108, Issue 3, Page(s) 533–542

Abstract: The methylenetetrahydrofolate reductase (MTHFR) 677 C→T polymorphism may be associated with elevated total homocysteine (tHcy) levels, an independent risk factor for cardiovascular disease. It was the study objective to evaluate in vivo lipid ... ...

Abstract	The methylenetetrahydrofolate reductase (MTHFR) 677 C→T polymorphism may be associated with elevated total homocysteine (tHcy) levels, an independent risk factor for cardiovascular disease. It was the study objective to evaluate in vivo lipid peroxidation and platelet activation in carriers of the MTHFR 677 C→T polymorphism and in non-carriers, in relation to tHcy and folate levels. A cross-sectional comparison of urinary 8-iso-prostaglandin (PG)F(2α) and 11-dehydro-thromboxane (TX)B(2) (markers of in vivo lipid peroxidation and platelet activation, respectively) was performed in 100 carriers and 100 non-carriers of the polymorphism. A methionine-loading test and folic acid supplementation were performed to investigate the causal relationship of the observed associations. Urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2) were higher in carriers with hyperhomocysteinaemia than in those without hyperhomocysteinaemia (p<0.0001). Hyperhomocysteinaemic carriers had lower folate levels (p=0.0006), higher urinary 8-iso-PGF(2α) (p<0.0001) and 11-dehydro-TXB(2) (p<0.0001) than hyperhomocysteinaemic non-carriers. On multiple regression analysis, high tHcy (p<0.0001), low folate (p<0.04) and MTHFR 677 C→T polymorphism (p<0.001) independently predicted high rates of 8-iso-PGF(2α) excretion. Methionine loading increased plasma tHcy (p=0.002), and both urinary prostanoid metabolites (p=0.002). Folic acid supplementation was associated with decreased urinary 8-iso-PGF(2α) and 11-dehydro-TXB2 excretion (p<0.0003) in the hyperhomocysteinaemic group, but not in the control group, with substantial inter-individual variability related to baseline tHcy level and the extent of its reduction. In conclusion, hyperhomocysteinaemia due to the MTHFR 677 C→T polymorphism is associated with enhanced in vivo lipid peroxidation and platelet activation that are reversible, at least in part, following folic acid supplementation. An integrated biomarker approach may help identifying appropriate candidates for effective folate supplementation.
MeSH term(s)	Biomarkers ; Cardiovascular Diseases/epidemiology ; Comorbidity ; Cross-Sectional Studies ; Diabetes Mellitus/epidemiology ; Dinoprost/analogs & derivatives ; Dinoprost/urine ; Dyslipidemias/epidemiology ; Folic Acid/blood ; Folic Acid/therapeutic use ; Homocystinuria/blood ; Homocystinuria/epidemiology ; Homocystinuria/genetics ; Humans ; Hyperhomocysteinemia/blood ; Hyperhomocysteinemia/drug therapy ; Hyperhomocysteinemia/epidemiology ; Hyperhomocysteinemia/genetics ; Lipid Peroxidation ; Methionine ; Methylenetetrahydrofolate Reductase (NADPH2)/blood ; Methylenetetrahydrofolate Reductase (NADPH2)/deficiency ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics ; Muscle Spasticity/blood ; Muscle Spasticity/epidemiology ; Muscle Spasticity/genetics ; Oxidative Stress ; Platelet Activation ; Polymorphism, Single Nucleotide ; Psychotic Disorders/blood ; Psychotic Disorders/epidemiology ; Psychotic Disorders/genetics ; Smoking/epidemiology ; Thromboxane B2/analogs & derivatives ; Thromboxane B2/urine
Chemical Substances	Biomarkers ; 8-epi-prostaglandin F2alpha (27415-26-5) ; Thromboxane B2 (54397-85-2) ; 11-dehydro-thromboxane B2 (67910-12-7) ; Folic Acid (935E97BOY8) ; Methionine (AE28F7PNPL) ; Dinoprost (B7IN85G1HY) ; Methylenetetrahydrofolate Reductase (NADPH2) (EC 1.5.1.20)
Language	English
Publishing date	2012-09
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	518294-3
ISSN	0340-6245
ISSN	0340-6245
DOI	10.1160/TH11-12-0899
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Article ; Online: Stress-induced salivary cortisol secretion during hypobaric hypoxia challenge and in vivo urinary thromboxane production in healthy male subjects.

Simeoni, Simona / Biselli, Roberto / D'Amelio, Raffaele / Rocca, Bianca / Lattanzio, Stefano / Mucci, Luciana / Davì, Giovanni / Patacchioli, Francesca Romana

Stress (Amsterdam, Netherlands)

2011 Volume 14, Issue 3, Page(s) 282–289

Abstract: Few studies have assessed the effects of stress on in vivo platelet activation. In the present study, hypobaric hypoxia induced by rapid decompression during high-altitude simulated flight in a hypobaric chamber was used to evaluate the effects of ... ...

Abstract	Few studies have assessed the effects of stress on in vivo platelet activation. In the present study, hypobaric hypoxia induced by rapid decompression during high-altitude simulated flight in a hypobaric chamber was used to evaluate the effects of environmental stress on salivary cortisol and urinary thromboxane metabolite (TXM) excretion, a noninvasive marker of in vivo platelet function. Twenty-one male aviators (mean ± SD age = 36 ± 7 years) experiencing hypoxia by removing their oxygen mask for 4-5 min during a simulated flight to 25,000 ft (7,620 m; pO(2) = 59.17 mmHg) and a matched control group of thirteen flying instructors wearing oxygen masks during the challenge, were studied. Hypobaric hypoxia induced a transient significant increase (P < 0.001) in the aviators' salivary cortisol concentration; the overall pattern of diurnal cortisol fluctuation was maintained in both groups. Urinary TXM showed a significant ∼30% reduction (P < 0.01) after the chamber session in aviators exposed to hypobaric hypoxia, but not in controls. A significant inverse correlation was found between salivary cortisol and urinary TXM in aviators (r = - 0.64, P = 0.0015). Salivary cortisol was a significant predictor (P < 0.001) for urinary TXM concentrations in aviators. In conclusion, here we observed that an acute stress-induced salivary cortisol increase was associated with reduced urinary thromboxane biosynthesis, providing the first indirect evidence for an inhibitory effect of acute stress on in vivo platelet function.
MeSH term(s)	Adult ; Altitude Sickness/physiopathology ; Dinoprost/analogs & derivatives ; Dinoprost/urine ; Humans ; Hydrocortisone/secretion ; Hypoxia/physiopathology ; Male ; Saliva/chemistry ; Stress, Physiological/physiology ; Thromboxane B2/analogs & derivatives ; Thromboxane B2/urine
Chemical Substances	8-epi-prostaglandin F2alpha (27415-26-5) ; Thromboxane B2 (54397-85-2) ; 11-dehydro-thromboxane B2 (67910-12-7) ; Dinoprost (B7IN85G1HY) ; Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2011-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1387706-9
ISSN	1607-8888 ; 1025-3890
ISSN (online)	1607-8888
ISSN	1025-3890
DOI	10.3109/10253890.2010.545458
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Article: Effects of atorvastatin and rosuvastatin on thromboxane-dependent platelet activation and oxidative stress in hypercholesterolemia

Puccetti, Luca / Santilli, Francesca / Pasqui, Anna Laura / Lattanzio, Stefano / Liani, Rossella / Ciani, Federica / Ferrante, Elisabetta / Ciabattoni, Giovanni / Scarpini, Francesca / Ghezzi, Anna / Auteri, Alberto / Davì, Giovanni

Atherosclerosis. 2011 Jan., v. 214, no. 1

2011

Abstract: OBJECTIVES: We examined the time-dependent effects of atorvastatin and rosuvastatin on in vivo oxidative stress and platelet activation, to assess whether these phenomena are related to any pleiotropic effect of any statin or to their LDL-lowering effect. ...

Abstract	OBJECTIVES: We examined the time-dependent effects of atorvastatin and rosuvastatin on in vivo oxidative stress and platelet activation, to assess whether these phenomena are related to any pleiotropic effect of any statin or to their LDL-lowering effect. We also asked whether the presence of specific allele frequencies in carriers of the 3′UTR/lectin-like oxidized LDL receptor-1 (LOX-1) polymorphism may influence the effect of either statin. METHODS: We included 60 hypercholesterolemic subjects, previously screened for LOX-1 3′UTR polymorphism, randomized, according to genetic profile (15 T and 15 C carriers for each arm), to atorvastatin 20mg/day or rosuvastatin 10mg/day. RESULTS: After 8 weeks, atorvastatin and rosuvastatin were associated with comparable, significant reductions in LDL cholesterol (40.8% and 43.6%, respectively), plasma hs-CRP (9.5% vs. 13.8%), urinary 11-dehydro-thromboxane (TX) B₂ (38.9% vs. 27.1%) and 8-iso-prostaglandin (PG) F₂α (39.4% vs. 19.4%). The impact of rosuvastatin or atorvastatin on CRP, 8-iso-PGF₂α, and 11-dehydro-TXB₂ did not differ according to the LOX-1 haplotype. On multiple regression analyses, only CRP and LDL were independent predictors of 11-dehydro-TXB₂, and only LDL was a significant predictor of 8-iso-PGF₂α. CONCLUSIONS: Both atorvastatin and rosuvastatin cause comparable reductions of thromboxane-dependent platelet activation, lipid peroxidation and inflammation. The presence of 3′UTR/LOX-1 polymorphism does not affect the changes induced by either statin.
Keywords	atherosclerosis ; gene frequency ; haplotypes ; hypercholesterolemia ; inflammation ; lipid peroxidation ; low density lipoprotein cholesterol ; oxidative stress ; platelet activation ; regression analysis
Language	English
Dates of publication	2011-01
Size	p. 122-128.
Publishing place	Elsevier Ireland Ltd
Document type	Article
ZDB-ID	80061-2
ISSN	1879-1484 ; 0021-9150
ISSN (online)	1879-1484
ISSN	0021-9150
DOI	10.1016/j.atherosclerosis.2010.10.006
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Article ; Online: Circulating myeloid-related protein-8/14 is related to thromboxane-dependent platelet activation in patients with acute coronary syndrome, with and without ongoing low-dose aspirin treatment.

Santilli, Francesca / Paloscia, Leonardo / Liani, Rossella / Di Nicola, Marta / Di Marco, Massimo / Lattanzio, Stefano / La Barba, Sara / Pascale, Silvia / Mascellanti, Marco / Davì, Giovanni

Journal of the American Heart Association

2014 Volume 3, Issue 4

Abstract: Background: Platelet activation is involved in acute coronary syndromes (ACS). Incomplete suppression by low-dose aspirin treatment of thromboxane (TX) metabolite excretion (urinary 11-dehydro-TXB2) is predictive of vascular events in high-risk patients. ...

Abstract	Background: Platelet activation is involved in acute coronary syndromes (ACS). Incomplete suppression by low-dose aspirin treatment of thromboxane (TX) metabolite excretion (urinary 11-dehydro-TXB2) is predictive of vascular events in high-risk patients. Myeloid-related protein (MRP)-8/14 is a heterodimer secreted on activation of platelets, monocytes, and neutrophils, regulating inflammation and predicting cardiovascular events. Among platelet transcripts, MRP-14 has emerged as a powerful predictor of ACS. Methods and results: We enrolled 68 stable ischemic heart disease (IHD) and 63 ACS patients, undergoing coronary angiography, to evaluate whether MRP-8/14 release in the circulation is related to TX-dependent platelet activation in ACS and IHD patients and to residual TX biosynthesis in low-dose aspirin-treated ACS patients. In ACS patients, plasma MRP-8/14 and urinary 11-dehydro-TXB2 levels were linearly correlated (r=0.651, P<0.001) but significantly higher than those in IHD patients (P=0.012, P=0.044) only among subjects not receiving aspirin. In aspirin-treated ACS patients, MRP-8/14 and 11-dehydro-TXB2 were lower versus those not receiving aspirin (P<0.001) and still significantly correlated (r=0.528, P<0.001). Higher 11-dehydro-TXB2 significantly predicted higher MRP-8/14 in both all ACS patients and ACS receiving aspirin (P<0.001, adj R(2)=0.463 and adj R(2)=0.497) after multivariable adjustment. Conversely, plasma MRP-8/14 (P<0.001) and higher urinary 8-iso-prostaglandin F2α (P=0.050) levels were significant predictors of residual, on-aspirin, TX biosynthesis in ACS (adjusted R(2)=0.384). Conclusions: Circulating MRP-8/14 is associated with TX-dependent platelet activation in ACS, even during low-dose aspirin treatment, suggesting a contribution of residual TX to MRP-8/14 shedding, which may further amplify platelet activation. Circulating MRP-8/14 may be a target to test different antiplatelet strategies in ACS.
MeSH term(s)	Acute Coronary Syndrome/blood ; Acute Coronary Syndrome/drug therapy ; Aged ; Aspirin/therapeutic use ; Calgranulin A/blood ; Calgranulin B/blood ; Chronic Disease ; Dinoprost/analogs & derivatives ; Dinoprost/urine ; Female ; Humans ; Male ; Middle Aged ; Myocardial Ischemia/blood ; Myocardial Ischemia/drug therapy ; Platelet Activation ; Platelet Aggregation Inhibitors/therapeutic use ; Thromboxane B2/analogs & derivatives ; Thromboxane B2/urine
Chemical Substances	Calgranulin A ; Calgranulin B ; Platelet Aggregation Inhibitors ; 8-epi-prostaglandin F2alpha (27415-26-5) ; Thromboxane B2 (54397-85-2) ; 11-dehydro-thromboxane B2 (67910-12-7) ; Dinoprost (B7IN85G1HY) ; Aspirin (R16CO5Y76E)
Language	English
Publishing date	2014-07-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.114.000903
Database	MEDical Literature Analysis and Retrieval System OnLINE

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