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September 26, 2012Journal of the American Heart AssociationOpen Access

Protein Kinase G Iα Inhibits Pressure Overload–Induced Cardiac Remodeling and Is Required for the Cardioprotective Effect of Sildenafil In Vivo

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Population

Wild-type mice and Leucine Zipper Mutant mice with selective mutations in the PKGIα leucine zipper…

Comparison

Phosphodiesterase 5 inhibition with sildenafil… vs Vehicle and/or wild-type controls

Design

Preclinical

Follow-up

up to 21 days

Authors

RBRobert M. BlantonETEiki TakimotoALAngela Lane

Discussion

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Overview

Caution against human extrapolation of sildenafil in pressure-overload HF; extends PKGIα as required effector for further mechanistic study.

Structured PICO

P
Population
Wild-type (WT) mice and Leucine Zipper Mutant (LZM) mice with selective mutations in the PKGIα leucine zipper interaction domain subjected to transaortic constriction (TAC)-induced left ventricular pressure overload.
I
Intervention
Phosphodiesterase 5 (PDE5) inhibition with sildenafil in the setting of transaortic constriction (TAC)
C
Comparator
Vehicle and/or wild-type controls
O
Outcome
Cardiac remodeling (LV systolic and diastolic dysfunction, pathologic hypertrophy), mortality, and congestive heart failuresurrogate

PKGIα plays a direct role in attenuating pressure overload-induced cardiac remodeling and is a required effector for the cardioprotective effects of sildenafil in vivo.

Cite This Study

Blanton et al. (2012) studied this question.

synapsesocial.com/papers/6a7a7342bdf697b3de02a3d8https://doi.org/10.1161/jaha.112.003731
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Also Consider

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

  1. 1Cardiac hypertrophy is not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytes2010 · 103 citations
  2. 2Cyclic GMP-dependent Protein Kinase Iα Attenuates Necrosis and Apoptosis Following Ischemia/Reoxygenation in Adult Cardiomyocyte2006 · 118 citations
  3. 3Inhibition of calcineurin-NFAT hypertrophy signaling by cGMP-dependent protein kinase type I in cardiac myocytes2002 · 278 citations
  4. 4Pressure overload-induced LV hypertrophy and dysfunction in mice are exacerbated by congenital NOS3 deficiency2004 · 115 citations
  5. 5Cardiomyocyte-restricted restoration of nitric oxide synthase 3 attenuates left ventricular remodeling after chronic pressure overload2007 · 72 citations