Phosphoinositide 3-kinase (p110 alpha) gene delivery limits diabetes-induced cardiac NADPH oxidase and cardiomyopathy in a mouse model with established diastolic dysfunction
Darnel Prakoso, Miles J De Blasio, Chengxue Qin, Sarah Rosli, Helen Kiriazis, Hongwei Qian, Xiao-Jun Du, Kate L Weeks, Paul Gregorevic, Julie R McMullen, Rebecca H Ritchie
CLINICAL SCIENCE | PORTLAND PRESS LTD | Published : 2017
Phosphoinositide 3-kinase [PI3K (p110α)] is able to negatively regulate the diabetes-induced increase in NADPH oxidase in the heart. Patients affected by diabetes exhibit significant cardiovascular morbidity and mortality, at least in part due to a cardiomyopathy characterized by oxidative stress and left ventricular (LV) dysfunction. Thus, PI3K (p110α) may represent a novel approach to protect the heart from diabetes-induced cardiac oxidative stress and dysfunction. In the present study, we investigated the therapeutic potential of a delayed intervention with cardiac-targeted PI3K gene therapy, administered to mice with established diabetes-induced LV diastolic dysfunction. Diabetes was ind..View full abstract
Awarded by National Heart Foundation of Australia
Awarded by senior research fellowships from the National Health and Medical Research Council
Awarded by Career Development Fellowship from the NHMRC
This work was supported by the National Heart Foundation of Australia [grant number G12M6486 (to R.H.R. and J.R.M.)]; the Victorian Government of Australia's Operational Infrastructure Support Program; senior research fellowships from the National Health and Medical Research Council [grant numbers ID1059960 (to R.H.R.), ID1043026 (to X.J.D.) and ID1078985 (to J.R.M.)]; Career Development Fellowship from the NHMRC [grant number ID1046782 (to P.G.)]; and the University of Melbourne (Melbourne International Research Scholarship and Melbourne International Fee Remission Scholarship (to D.P.).