Myocardial-restricted ablation of the GTPase RAD results in a pro-adaptive heart response in mice.

ABSTRACT: Existing therapies to improve heart function target β-adrenergic receptor (β-AR) signaling and Ca²⁺ handling and often lead to adverse outcomes. This underscores an unmet need for positive inotropes that improve heart function without any adverse effects. The GTPase Ras associated with diabetes (RAD) regulates L-type Ca²⁺ channel (LTCC) current (I_Ca,L). Global RAD-knockout mice (gRAD^-/-) have elevated Ca²⁺ handling and increased cardiac hypertrophy, but RAD is expressed also in noncardiac tissues, suggesting the possibility that pathological remodeling is due also to noncardiac effects. Here, we engineered a myocardial-restricted inducible RAD-knockout mouse (RAD^Δ/Δ). Using an array of methods and techniques, including singl

SUBMITTER: Ahern BM 

PROVIDER: S-EPMC6635439 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature