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...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.展开更多
基金Supported by The University of Colorado-Denver Center for Women’s Health Research(to Walker LA)NIH NHLBI HL007822-19(to Bruns DR)+1 种基金NIH NHLBI HL117724(to Autieri MV)NIH NHLBI HL115575(to Autieri MV)
文摘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.
