TY - JOUR
T1 - Comparative effects of torasemide and furosemide on gap junction proteins and cardiac fibrosis in a rat model of dilated cardiomyopathy
AU - Watanabe, Kenichi
AU - Sreedhar, Remya
AU - Thandavarayan, Rajarajan A.
AU - Karuppagounder, Vengadeshprabhu
AU - Giridharan, Vijayasree V.
AU - Antony, Shanish
AU - Harima, Meilei
AU - Nakamura, Masahiko
AU - Suzuki, Kenji
AU - Suzuki, Hiroshi
AU - Sone, Hirohito
AU - Arumugam, Somasundaram
N1 - Publisher Copyright:
© 2016 International Union of Biochemistry and Molecular Biology
PY - 2017/3/1
Y1 - 2017/3/1
N2 - Cardiac fibrosis is the major hallmark of adverse cardiac remodeling in chronic heart failure (CHF) and its therapeutic targeting might help against cardiac dysfunction during chronic conditions. Diuretic agents are potentially useful in these cases, but their effects on the cardiac fibrosis pathogenesis are yet to be identified. This study was designed to identify and compare the effects of diuretic drugs torasemide and furosemide on cardiac fibrosis in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin mediated experimental autoimmune myocarditis. Gap junction proteins, connexin-43 and N-cadherin, expressions were downregulated in the hearts of CHF rats, while torasemide treatment has upregulated their expression. Western blotting and immunohistochemical analysis for various cardiac fibrosis related proteins as well as histopathological studies have shown that both drugs have potential anti-fibrotic effects. Among them, torasemide has superior efficacy in offering protection against adverse cardiac remodeling in the selected rat model of dilated cardiomyopathy. In conclusion, torasemide treatment has potential anti-fibrotic effect in the hearts of CHF rats, possibly via improving the gap junction proteins expression and thereby improving the cell–cell interaction in the heart.
AB - Cardiac fibrosis is the major hallmark of adverse cardiac remodeling in chronic heart failure (CHF) and its therapeutic targeting might help against cardiac dysfunction during chronic conditions. Diuretic agents are potentially useful in these cases, but their effects on the cardiac fibrosis pathogenesis are yet to be identified. This study was designed to identify and compare the effects of diuretic drugs torasemide and furosemide on cardiac fibrosis in a rat model of dilated cardiomyopathy induced by porcine cardiac myosin mediated experimental autoimmune myocarditis. Gap junction proteins, connexin-43 and N-cadherin, expressions were downregulated in the hearts of CHF rats, while torasemide treatment has upregulated their expression. Western blotting and immunohistochemical analysis for various cardiac fibrosis related proteins as well as histopathological studies have shown that both drugs have potential anti-fibrotic effects. Among them, torasemide has superior efficacy in offering protection against adverse cardiac remodeling in the selected rat model of dilated cardiomyopathy. In conclusion, torasemide treatment has potential anti-fibrotic effect in the hearts of CHF rats, possibly via improving the gap junction proteins expression and thereby improving the cell–cell interaction in the heart.
KW - cardiac fibrosis
KW - connexin-43
KW - furosemide
KW - gap junction
KW - torasemide
UR - http://www.scopus.com/inward/record.url?scp=84988905806&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84988905806&partnerID=8YFLogxK
U2 - 10.1002/biof.1332
DO - 10.1002/biof.1332
M3 - Article
C2 - 27662823
AN - SCOPUS:84988905806
SN - 0951-6433
VL - 43
SP - 187
EP - 194
JO - BioFactors
JF - BioFactors
IS - 2
ER -