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.

Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy / Di Luigi, Luigi; Corinaldesi, Clarissa; Colletti, Marta; Scolletta, Sabino; Antinozzi, Cristina; Vannelli, Gabriella B; Giannetta, Elisa; Gianfrilli, Daniele; Isidori, Andrea M; Migliaccio, Silvia; Poerio, Noemi; Fraziano, Maurizio; Lenzi, Andrea; Crescioli, Clara. - In: INFLAMMATION. - ISSN 0360-3997. - ELETTRONICO. - 39:(2016), pp. 1238-1252. [10.1007/s10753-016-0359-6]

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

CRESCIOLI, CLARA
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.
2016
39
1238
1252
Di Luigi, Luigi; Corinaldesi, Clarissa; Colletti, Marta; Scolletta, Sabino; Antinozzi, Cristina; Vannelli, Gabriella B; Giannetta, Elisa; Gianfrilli, Daniele; Isidori, Andrea M; Migliaccio, Silvia; Poerio, Noemi; Fraziano, Maurizio; Lenzi, Andrea; Crescioli, Clara
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1050757
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