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March 17, 2010Cardiovascular ResearchOpen Access

Constitutive glycogen synthase kinase-3α/β activity protects against chronic β-adrenergic remodelling of the heart

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Why the study?

Does constitutive GSK-3alpha/beta activity protect against chronic beta-adrenergic remodeling of the heart in mice?

Population

Knockin mice lacking the critical N-terminal serines, 21 of GSK-3alpha and 9 of GSK-3beta respectively, and…

Comparison

Chronic subcutaneous isoproterenol infusion over… vs Wild-type mice receiving the same chronic…

Design

Preclinical

Follow-up

14 days

Authors

IWIan WebbYNYasuhiro NishinoJCJames Clark

Discussion

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Overview

Constitutive GSK-3 activity attenuates ISO remodeling in mice; hypothesis-generating for human therapeutic targeting.

Structured PICO

Does constitutive GSK-3alpha/beta activity protect against chronic beta-adrenergic remodeling of the heart in mice?

P
Population
Knockin (KI) mice lacking the critical N-terminal serines, 21 of GSK-3alpha and 9 of GSK-3beta respectively, and wild-type (WT) mice
I
Intervention
Chronic subcutaneous isoproterenol (ISO) infusion over 14 days
C
Comparator
Wild-type (WT) mice receiving the same chronic subcutaneous ISO infusion
O
Outcome
Cardiac hypertrophy, interstitial fibrosis, and impaired contractilitysurrogate

Expression of inactivation-resistant GSK-3alpha/beta protects against pathological hypertrophy induced by chronic adrenergic stimulation, suggesting a potential therapeutic target for preventing adverse cardiac remodeling.

Cite This Study

Webb et al. (2010) studied this question.

synapsesocial.com/papers/6a707fa1ac440176ef2928b2https://doi.org/10.1093/cvr/cvq061
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Myocardial stress remodelling after regional infarction is independent of glycogen synthase kinase-3 inactivation2010 · 14 citations
  2. 2GSK-3α directly regulates β-adrenergic signaling and the response of the heart to hemodynamic stress in mice2010 · 67 citations
  3. 3Glycogen Synthase Kinase-3β Regulates Post–Myocardial Infarction Remodeling and Stress-Induced Cardiomyocyte Proliferation In Vivo2010 · 120 citations
  4. 4Distinct roles of GSK-3α and GSK-3β phosphorylation in the heart under pressure overload2008 · 137 citations
  5. 5Glycogen Synthase Kinase-3α Reduces Cardiac Growth and Pressure Overload-induced Cardiac Hypertrophy by Inhibition of Extracellular Signal-regulated Kinases2007 · 68 citations