title: Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy.
abstract: T helper 1 (Th1) type cytokines and chemokines are bioactive mediators in inflammation underling several diseases and co-morbid conditions, such as cardiovascular and metabolic disorders. Th1 chemokine CXCL10 participates in heart damage initiation/progression; cardioprotection has been recently associated with sildenafil, a type 5 phosphodiesterase inhibitor. We aimed to evaluate the effect of sildenafil on CXCL10 in inflammatory conditions associated with diabetic cardiomyopathy. We analyzed: CXCL10 gene and protein in human cardiac, endothelial, and immune cells challenged by pro-inflammatory stimuli with and without sildenafil; serum CXCL10 in diabetic subjects at cardiomyopathy onset, before and after 3 months of treatment with sildenafil vs. placebo. Sildenafil significantly decreased CXCL10 protein secretion (IC50 = 2.6 × 10(-7)) and gene expression in human cardiomyocytes and significantly decreased circulating CXCL10 in subjects with chemokine basal level ≥ 930 pg/ml, the cut-off value as assessed by ROC analysis. In conclusion, sildenafil could be a pharmacologic tool to control CXCL10-associated inflammation in diabetic cardiomyopathy.
authors.affiliation: Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Luigi
authors.affiliation: Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Corinaldesi
authors.affiliation: Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Colletti
authors.affiliation: Department of Medical Biotechnologies, Anesthesia and Intensive Care, University of Siena, Siena, Italy.
authors.forename: Sabino
authors.initials: S
authors.lastname: Scolletta
authors.affiliation: Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Antinozzi
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Gabriella B
authors.initials: GB
authors.lastname: Vannelli
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Giannetta
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Gianfrilli
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Isidori
authors.affiliation: Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Migliaccio
authors.affiliation: Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Noemi
authors.initials: N
authors.lastname: Poerio
authors.affiliation: Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fraziano
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lenzi
authors.affiliation: Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy. clara.crescioli@uniroma4.it.
authors.forename: Clara
authors.initials: C
authors.lastname: Crescioli
mesh_terms: D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy / Q000473:pathology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D032383:Myocytes, Cardiac / Q000378:metabolism*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D000068677:Sildenafil Citrate / Q000494:pharmacology*
chemical_list: D054357:Chemokine CXCL10; D058986:Phosphodiesterase 5 Inhibitors; D000068677:Sildenafil Citrate
keywords: CXCL10; PDE5 inhibition; T helper 1; cardiomyopathy; inflammation