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Open Access 01-06-2016 | ORIGINAL ARTICLE

Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy

Authors: Luigi Di Luigi, Clarissa Corinaldesi, Marta Colletti, Sabino Scolletta, Cristina Antinozzi, Gabriella B. Vannelli, Elisa Giannetta, Daniele Gianfrilli, Andrea M. Isidori, Silvia Migliaccio, Noemi Poerio, Maurizio Fraziano, Andrea Lenzi, Clara Crescioli

Published in: Inflammation | Issue 3/2016

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.

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Title: Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy
Authors: Luigi Di Luigi
Clarissa Corinaldesi
Marta Colletti
Sabino Scolletta
Cristina Antinozzi
Gabriella B. Vannelli
Elisa Giannetta
Daniele Gianfrilli
Andrea M. Isidori
Silvia Migliaccio
Noemi Poerio
Maurizio Fraziano
Andrea Lenzi
Clara Crescioli
Publication date: 01-06-2016
Publisher: Springer US
Published in: Inflammation / Issue 3/2016
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-016-0359-6

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Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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Other articles of this Issue 3/2016

Impaired Ca2+ Homeostasis and Decreased Orai1 Expression Modulates Arterial Hyporeactivity to Vasoconstrictors During Endotoxemia

Does Inflammation Mediate the Association Between Obesity and Insulin Resistance?

Preliminary Study on Gene Expression of Chitinase-Like Cytokines in Human Airway Epithelial Cell Under Chitin and Chitosan Microparticles Treatment

The Effects of IL-22 on the Inflammatory Mediator Production, Proliferation, and Barrier Function of HUVECs

Dynamic Analysis of Changes of Protein Levels and Selected Biochemical Indices in Rat Serum in the Course of Experimental Pleurisy

Leukocyte Infiltration Triggers Seizure Recurrence in a Rat Model of Temporal Lobe Epilepsy

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