Cardioprotective role of sodium thiosulfate on chronic heart failure by modulating endogenous H2S generation.
OBJECTIVE
Sodium thiosulfate (STS) has been shown to be an antioxidant and calcium solubilizer, but the possible role of STS in dysfunctional ventricles remains unknown. Here, we assessed the effects of STS in the failing heart.


METHODS
Heart failure was created by an arteriovenous fistula (AVF). Mice were divided into 4 groups: sham, AVF, sham + STS, and AVF + STS. STS (3 mg/ml) was supplemented with drinking water for 6 weeks in the appropriate surgery groups after surgery.


RESULTS
M-mode echocardiograms showed ventricular contractile dysfunction with reduced aortic blood flow in AVF mice, whereas STS treatment prevented the decline in cardiac function. Ventricular collagen, MMP-2 and -9, and TIMP-1 were robustly increased with a decreasing trend in adenylate cyclase VI expression; however, STS supplementation reversed these effects in AVF mice. Among 2 enzymes that produce endogenous hydrogen sulfide (H(2)S), cystathionine-gamma-lyase (CSE) expression was attenuated in AVF mice with no changes in cystathionine-beta-synthase (CBS) expression. In addition, reduced production of H(2)S in AVF ventricular tissue was normalized with STS supplementation. Moreover, cardiac tissues were more responsive to H(2)S when AVF mice were supplemented with STS compared to AVF alone.


CONCLUSIONS
These results suggested that STS modulated cardiac dysfunction and the extracellular matrix, in part, by increasing ventricular H(2)S generation.
Sen
Utpal
U
Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Vacek
Thomas P
TP
Hughes
William M
WM
Kumar
Munish
M
Moshal
Karni S
KS
Tyagi
Neetu
N
Metreveli
Naira
N
Hayden
Melvin R
MR
Tyagi
Suresh C
SC
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000503:physiopathology; D001164:Arteriovenous Fistula; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002908:Chronic Disease; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000187:drug effects / Q000378:metabolism; D004452:Echocardiography; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000187:drug effects; D013885:Thiosulfates / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000187:drug effects / Q000378:metabolism
D002316:Cardiotonic Agents; D013885:Thiosulfates; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D003542:Cystathionine gamma-Lyase; D000262:Adenylyl Cyclases; C017717:sodium thiosulfate; D006862:Hydrogen Sulfide