title: Endothelial dysfunction markers as a therapeutic target for Sildenafil treatment and effects on metabolic control in type 2 diabetes.
abstract: OBJECTIVE
  Endothelial dysfunction (ED) plays a role in diabetic cardiovascular complications. Hyperglycemia increases cytockines involved in vascular inflammation. Inhibition of phosphodiesterase type 5 (PDE5) exerts a relaxation on corpora cavernosa and has cardioprotective properties. The effect of chronic sildenafil treatment, on ED markers and metabolic parameters in a non-randomized study on men with type 2 diabetes (T2DM), was investigated.
  
  
  METHODS
  Twenty-eight T2DM patients (61.2 ± 7.8 years, hemoglobin A1c (HbA1c) 7.9 ± 1.3%, duration of diabetes 11.5 ± 7.8 years) were treated with sildenafil 100 mg/d for 3 months. Baseline and postprandial glycemia, insulin, HbA1c, HOMA index, lipids, glomerular filtration rate, homocysteine were assessed at each visit. P-selectin (CD62P), CD14/42b, CD14/41, ICAM (CD54), PECAM (CD31) and CD11b/CD18, were evaluated, after monocyte isolation with flow-cytometry, before and after treatment.
  
  
  RESULTS
  After 3 months, sildenafil decreased P-selectin (p < 0.05), post-prandial glycemia (p < 0.01), HbA1c (p < 0.01), low-density lipoprotein cholesterol (p < 0.01) and increased high-density lipoprotein (p < 0.05).
  
  
  CONCLUSIONS
  PDE5 inhibition, in T2DM patients, reduces the endothelial function marker P-selectin and exerts a beneficial effect on glycometabolic control.
authors.affiliation: a 1 Sapienza University of Rome, Policlinico Umberto I, Department of Experimental Medicine , Viale del Policlinico 155, 00161, Rome, Italy +390 649 978 381 ; +390 649 978 381 ; susanna.morano@uniroma1.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Mandosi
authors.affiliation: a 1 Sapienza University of Rome, Policlinico Umberto I, Department of Experimental Medicine , Viale del Policlinico 155, 00161, Rome, Italy +390 649 978 381 ; +390 649 978 381 ; susanna.morano@uniroma1.it.
authors.forename: Elisa
authors.initials: E
authors.lastname: Giannetta
authors.affiliation: a 1 Sapienza University of Rome, Policlinico Umberto I, Department of Experimental Medicine , Viale del Policlinico 155, 00161, Rome, Italy +390 649 978 381 ; +390 649 978 381 ; susanna.morano@uniroma1.it.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Filardi
authors.affiliation: a 1 Sapienza University of Rome, Policlinico Umberto I, Department of Experimental Medicine , Viale del Policlinico 155, 00161, Rome, Italy +390 649 978 381 ; +390 649 978 381 ; susanna.morano@uniroma1.it.
authors.forename: Manuela
authors.initials: M
authors.lastname: Lococo
authors.affiliation: a 1 Sapienza University of Rome, Policlinico Umberto I, Department of Experimental Medicine , Viale del Policlinico 155, 00161, Rome, Italy +390 649 978 381 ; +390 649 978 381 ; susanna.morano@uniroma1.it.
authors.forename: Camilla
authors.initials: C
authors.lastname: Bertolini
authors.affiliation: a 1 Sapienza University of Rome, Policlinico Umberto I, Department of Experimental Medicine , Viale del Policlinico 155, 00161, Rome, Italy +390 649 978 381 ; +390 649 978 381 ; susanna.morano@uniroma1.it.
authors.forename: Mara
authors.initials: M
authors.lastname: Fallarino
authors.affiliation: a 1 Sapienza University of Rome, Policlinico Umberto I, Department of Experimental Medicine , Viale del Policlinico 155, 00161, Rome, Italy +390 649 978 381 ; +390 649 978 381 ; susanna.morano@uniroma1.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Gianfrilli
authors.affiliation: b 2 Sapienza University, Departement of Histology and Embryology , Rome, Italy.
authors.forename: Mary Anna
authors.initials: MA
authors.lastname: Venneri
authors.affiliation: a 1 Sapienza University of Rome, Policlinico Umberto I, Department of Experimental Medicine , Viale del Policlinico 155, 00161, Rome, Italy +390 649 978 381 ; +390 649 978 381 ; susanna.morano@uniroma1.it.
authors.forename: Luisa
authors.initials: L
authors.lastname: Lenti
authors.affiliation: a 1 Sapienza University of Rome, Policlinico Umberto I, Department of Experimental Medicine , Viale del Policlinico 155, 00161, Rome, Italy +390 649 978 381 ; +390 649 978 381 ; susanna.morano@uniroma1.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lenzi
authors.affiliation: a 1 Sapienza University of Rome, Policlinico Umberto I, Department of Experimental Medicine , Viale del Policlinico 155, 00161, Rome, Italy +390 649 978 381 ; +390 649 978 381 ; susanna.morano@uniroma1.it.
authors.forename: Susanna
authors.initials: S
authors.lastname: Morano
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D006442:Glycated Hemoglobin; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D007328:Insulin / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D000068677:Sildenafil Citrate / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D008055:Lipids; D019007:P-Selectin; D058986:Phosphodiesterase 5 Inhibitors; D000068677:Sildenafil Citrate; D014665:Vasodilator Agents
keywords: P-selectin; phosphodiesterase type-5 inhibitors; sildenafil; type 2 diabetes