What is the clinical evidence from this study?

Study design: Review. Population: Cardiovascular function and disease. Intervention: PI3Kgamma. Primary outcome: Cardiac contractility.

What question did this study set out to answer?

Determine the functional role and downstream signaling mechanisms of phosphoinositide 3-kinase gamma (PI3Kγ) in modulating cardiac contractility and response to receptor stimulation.

April 1, 2004Biochemical Society Transactions

Phosphoinositide 3-kinase γ: kinase-dependent and -independent activities in cardiovascular function and disease

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Key result

PI3Kgamma negatively controls cardiac contractility through various signaling mechanisms, suggesting it as a potential drug target for critical cardiac pathologies like infarction or heart failure.

Population

Mice and cardiomyocytes with deletion of PI3Kgamma expression

Design

Review

Authors

GAGiuseppe AlloattiAzienda Sanitaria Locale di Asti GMGiuseppe MontrucchioUniversity of Parma GLGiuseppe LemboGeneral Cardiology

Discussion

Member takes

Implication

No immediate change to HF or MI management; leaves open targeted PI3Kγ inhibition trials to test therapeutic potential.

Key Points

Determine the functional role and downstream signaling mechanisms of phosphoinositide 3-kinase gamma (PI3Kγ) in modulating cardiac contractility and response to receptor stimulation.
Assessed basal cardiovascular parameters, including heart rate and blood pressure, alongside contractile force in PI3Kγ-knockout mice.
Measured cAMP accumulation in mutant cardiomyocytes exposed to beta-adrenergic agonists.
Examined downstream signaling cascades, including G(i)-coupled platelet-activating factor receptor activation, Akt phosphorylation, and NOSIII-mediated nitric oxide production.
PI3Kγ deletion maintained baseline heart rate and blood pressure but elevated cardiac contractility and increased cAMP production in response to beta-adrenergic stimulation.
Activation of PI3Kγ downstream of platelet-activating factor promoted Akt phosphorylation and NOSIII activation, stimulating nitric oxide synthesis to induce cardiodepression.
PI3Kγ mediated negative control of cardiac contractility across divergent G-protein-coupled receptor pathways, identifying it as a regulatory hub in ischemic and failing myocardium.

Structured PICO

Population

Mice and cardiomyocytes with deletion of PI3Kgamma expression

PI3Kgamma negatively regulates cardiac contractility through multiple signaling pathways, highlighting it as a potential therapeutic target for heart failure and myocardial infarction.

Cite This Study

Alloatti et al. (2004) conducted a review in Cardiovascular function and disease. PI3Kgamma was evaluated on Cardiac contractility. PI3Kgamma negatively controls cardiac contractility through various signaling mechanisms, suggesting it as a potential drug target for critical cardiac pathologies like infarction or heart failure.

synapsesocial.com/papers/6a93a98540aff459acebc1c3 https://doi.org/10.1042/bst0320383

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Phosphoinositide 3-kinase γ: kinase-dependent and -independent activities in cardiovascular function and disease

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Phosphoinositide 3-kinase γ: kinase-dependent and -independent activities in cardiovascular function and disease

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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