Gene therapy targeting cardiac phosphoinositide 3-kinase (p110 alpha) attenuates cardiac remodeling in type 2 diabetes
Darnel Prakoso, Miles J De Blasio, Mitchel Tate, Helen Kiriazis, Daniel G Donner, Hongwei Qian, David Nash, Minh Deo, Kate L Weeks, Laura J Parry, Paul Gregorevic, Julie R McMullen, Rebecca Helen Ritchie
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | AMER PHYSIOLOGICAL SOC | Published : 2020
Diabetic cardiomyopathy is a distinct form of heart disease that represents a major cause of death and disability in diabetic patients, particularly, the more prevalent type 2 diabetes patient population. In the current study, we investigated whether administration of recombinant adeno-associated viral vectors carrying a constitutively active phosphoinositide 3-kinase (PI3K)(p110α) construct (rAAV6-caPI3K) at a clinically relevant time point attenuates diabetic cardiomyopathy in a preclinical type 2 diabetes (T2D) model. T2D was induced by a combination of a high-fat diet (42% energy intake from lipid) and low-dose streptozotocin (three consecutive intraperitoneal injections of 55 mg/kg body..View full abstract
Awarded by National Health and Medical Research Council of Australia
This work was supported by a grant to M.J.D. from the CASS Foundation and, in part, by an infrastructure grant to the Baker Heart and Diabetes Institute from the Victorian Government of Australia. P.G. (ID1046782), R.H.R. (ID1059960), and J.R.M. (ID1078985) are supported by Senior Research Fellowships from the National Health and Medical Research Council of Australia. D.P. is supported by the University of Melbourne International Research Scholarship, Melbourne International Fee Remission Scholarship, and The Albert Shimmins Fund.