Decreased Soluble Guanylate Cyclase Contributes to Cardiac Dysfunction Induced by Chronic Doxorubicin Treatment in Mice.

ABSTRACT:

Aims

The use of doxorubicin, a potent chemotherapeutic agent, is limited by cardiotoxicity. We tested the hypothesis that decreased soluble guanylate cyclase (sGC) enzyme activity contributes to the development of doxorubicin-induced cardiotoxicity.

Results

Doxorubicin administration (20 mg/kg, intraperitoneally [IP]) reduced cardiac sGC activity in wild-type (WT) mice. To investigate whether decreased sGC activity contributes to doxorubicin-induced cardiotoxicity, we studied mice with cardiomyocyte-specific deficiency of the sGC α1-subunit (mice with cardiomyocyte-specific deletion of exon 6 of the sGCα1 allele [sGCα1^-/-CM]). After 12 weeks of doxorubicin administration (2 mg/kg/week IP), left ventricular (LV) systolic dysfunction was greater in sGCα1^-/-CM</

SUBMITTER: Vandenwijngaert S 

PROVIDER: S-EPMC5278809 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature