Carbohydrate sulfotransferase 15 (CHST15) is a
sulfotransferase responsible for biosynthesis of
chondroitin sulfate E (CS-E), which plays important roles in numerous biological events such as biosynthesis of proinflammatory
cytokines. However, the effects of CHST15
siRNA in rats with chronic
heart failure (CHF) after experimental autoimmune
myocarditis (EAM) have not yet been investigated. CHF was elicited in Lewis rats by immunization with
cardiac myosin, and after immunization, the rats were divided into two groups and treated with either CHST15
siRNA (2μg/week) or vehicle. Age matched normal rats without immunizations were also included in this study. After 7weeks of treatment, we investigated the effects of CHST15
siRNA on cardiac function, proinflammatory
cytokines, and cardiac remodeling in EAM rats. Myocardial functional parameters measured by hemodynamic and echocardiographic studies were significantly improved by CHST15
siRNA treatment in rats with CHF compared with that of vehicle-treated CHF rats. CHST15
siRNA significantly reduced cardiac
fibrosis, and
hypertrophy and its marker molecules (left ventricular (LV)
mRNA expressions of
transforming growth factor beta1,
collagens I and III, and
atrial natriuretic peptide) compared with vehicle-treated CHF rats. CHF-induced increased myocardial
mRNA expressions of proinflammatory
cytokines [
interleukin (IL)-6, IL-1β],
monocyte chemoattractant protein-1, and
matrix metalloproteinases (MMP-2 and -9), and CHST15 were also suppressed by the treatment with CHST15
siRNA. Western blotting study has confirmed the results obtained from
mRNA analysis as CHST15
siRNA treated rats expressed reduced levels of inflammatory and cardiac remodeling marker
proteins. Our results demonstrate for the first time, that CHST15
siRNA treatment significantly improved LV function and ameliorated the progression of cardiac remodeling in rats with CHF after EAM.