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

• Published in: Inflammation Vol. 39; no. 3; pp. 1238 - 1252
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2016; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Cells, Cultured; Chemokine CXCL10 - analysis; Chemokine CXCL10 - drug effects; Chemokine CXCL10 - genetics; Diabetic Cardiomyopathies - drug therapy; Diabetic Cardiomyopathies - pathology; Gene Expression - drug effects; Humans; Immunology; Inflammation - drug therapy; Internal Medicine; Myocytes, Cardiac - metabolism; Original; Original Article; Pathology; Pharmacology/Toxicology; Phosphodiesterase 5 Inhibitors - pharmacology; Rheumatology; Sildenafil Citrate - pharmacology; T helper 1; CXCL10; cardiomyopathy; PDE5 inhibition; inflammation
• ISSN: 0360-3997; 1573-2576; 1573-2576
• DOI: 10.1007/s10753-016-0359-6

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 (IC 50  = 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.