Key result
PI3Kγ inactivation or inhibition reduces cardiac fibrosis and preserves LV function in mice.
Why the study?
The distinct contributions of bone marrow-derived and cardiac PI3Kγ activity to pressure overload-induced heart failure and maladaptive remodeling were not fully understood.
Does PI3Kγ inactivation or inhibition prevent maladaptive remodeling and preserve cardiac function in a mouse model of pressure overload-induced heart failure?
Population
Mice subjected to transverse aortic constriction including wild-type, PI3Kγ KD knock-in, and bone marrow chimeras
Comparison
PI3Kγ KD knock-in or selective PI3Kγ inhibitor treatment versus wild-type controls
Design
Preclinical study using genetic knock-in and bone marrow chimera models
Follow-up
Up to 16 weeks
Authors
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Does not support clinical use; hypothesis-generating for PI3Kγ inhibition in pressure-overload HF.
Does PI3Kγ inactivation or inhibition prevent maladaptive remodeling and preserve cardiac function in a mouse model of pressure overload-induced heart failure?
PI3Kγ contributes to maladaptive cardiac remodeling after pressure overload by modulating both cardiac and immune cell functions, suggesting PI3Kγ inhibition as a potential therapeutic strategy for heart failure.
Damilano et al. (2011) studied Pressure overload-induced heart failure. Catalytically inactive PI3Kγ (PI3Kγ KD) or selective PI3Kγ inhibitor vs. Wild-type controls was evaluated on Cardiac fibrosis and function (left ventricular dilation, fractional shortening). Inactivation or inhibition of PI3Kγ in mice reduced fibrosis, prevented left ventricular dilation, and preserved cardiac function up to 16 weeks after transverse aortic constriction.
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