AIM To investigate the role of interleukin-19(IL-19) in a murine model of female-dominant heart failure(HF).METHODS Expression of one copy of a phosphorylation-deficient cyclic adenosine monophosphate response-element binding protein(dn CREB) causes HF, with accelerated morbidity and mortality in female mice compared to males. We assessed expression of IL-19, its receptor isoforms IL-20 R α/β, and downstream IL-19 signaling in this model of female-dominant HF. To test the hypothesis that IL-19 is cardioprotective in dn CREB-mediated HF, we generated a novel double transgenic(DTG) mouse of dn CREB and IL-19 knockout and assessed cardiac morbidity by echocardiography and survival of male and female mice.RESULTS IL-19 is expressed in the murine heart with decreased expression in dn CREB female compared to male mice. Further, the relative expression of the two IL-19 receptor isoforms manifests differently in the heart by sex and by disease. Male DTG mice had accelerated mortality and cardiac morbidity compared to dn CREB males, while female DTG mice showed no additional detriment, supporting the hypothesis that IL-19 is cardioprotective in this model. CONCLUSION Together, these data suggest IL-19 is an important cytokine mediating sex-specific cardiac(dys) function. Ongoing investigations will elucidate the mechanism(s) of sex-specific IL-19 mediated cardiac remodeling. AIM To investigate the role of interleukin-19 (IL-19) in a murine model of female-dominant heart failure (HF). METHODS Expression of one copy of a phosphorylation-deficient cyclic adenosine monophosphate response-element binding protein (dn CREB) Causes HF, with accelerated morbidity and mortality in female mice compared to males. We assessed expression of IL-19, its receptor isoforms IL-20 R α / β, and downstream IL-19 signaling in this model of female-dominant HF. To test the hypothesis that IL-19 is cardioprotective in dn CREB-mediated HF, we generated a novel double transgenic (DTG) mouse of dn CREB and IL-19 knockout and assessed cardiac morbidity by echocardiography and survival of male and female mice. RESULTS IL -19 is expressed in the murine heart with decreased expression in dn CREB female compared to male mice. Further, the relative expression of the two IL-19 receptor isoforms manifests differently in the heart by sex and by disease. Male DTG mice had accelerated mortality and car diac morbidity compared to dn CREB males, while female DTG mice showed no additional detriment, supporting the hypothesis that IL-19 is cardioprotective in this model. CONCLUSION Together, these data suggest IL-19 is an important cytokine mediating sex-specific cardiac (dys Ongoing investigations will elucidate the mechanism (s) of sex-specific IL-19 mediated cardiac remodeling.