Enhanced Cardiac Phosphoinositide 3-Kinase (p110 α) using Gene Therapy Attenuates Cardiac Remodeling in Type 2 Diabetic Mice.

Enhanced Cardiac Phosphoinositide 3-Kinase (p110α) using Gene Therapy Attenuates Cardiac Remodeling in Type 2 Diabetic Mice. Am J Physiol Heart Circ Physiol. 2020 Mar 06;: Authors: Prakoso D, De Blasio MJ, Tate M, Kiriazis H, Donner DG, Qian H, Nash D, Deo M, Weeks KL, Parry LJ, Gregorevic P, McMullen JR, Ritchie RH Abstract 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 diabetic population. In the current study, we investigated administration of recombinant adeno-associated viral vectors carrying a constitutively-active PI3K(p110α) construct (rAAV6-caPI3K) at a clinically-relevant time point attenuates diabetic cardiomyopathy in a pre-clinical type-2 diabetes (T2D) model. T2D was induced by a combination of high-fat diet and low-dose streptozotocin, and confirmed by increased body weight, hyperglycemia, and impaired glucose tolerance. After 18 weeks of untreated diabetes, impaired left ventricular (LV) systolic dysfunction was evident, as confirmed by echocardiography. A single tail vein injection of rAAV6-caPI3K gene therapy was then administered. Mice were followed for an additional 8 weeks before end-point. Administration of cardiac targeted rAAV6-caPI3K attenuates diabetes-induced cardiac remodeling by limiting cardiac fibrosis and cardiomyocyte hypertrophy. The diabetes-induced LV systolic dysfunctio...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research