Evidence map›Paper›PMID 22865386›Full record

ArticleAmerican journal of physiology. Heart and circulatory physiology2012

Diabetes-induced increased oxidative stress in cardiomyocytes is sustained by a positive feedback loop involving Rho kinase and PKCβ2.

Hesham Soliman, Anthony Gador, Yi-Hsuan Lu, Guorong Lin, Girish Bankar, Kathleen M MacLeod

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In one paragraph

Article in American journal of physiology. Heart and circulatory physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.2field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 42 citations in OpenAlex.

  1. Role of AMP deaminase in diabetic cardiomyopathy.Molecular and cellular biochemistry · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Hesham SolimanMolecular and Cellular Pharmacology Research Group, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
Anthony Gador
Yi-Hsuan Lu
Guorong Lin
Girish Bankar
Kathleen M MacLeod
University of British Columbia · CA

Funding

Canadian Institutes of Health Research MOP 97861
6 · The paper itself

Abstract

We previously reported that acute inhibition of the RhoA/Rho kinase (ROCK) pathway normalized contractile function of diabetic rat hearts, but the underlying mechanism is unclear. Protein kinase C (PKC) β(2) has been proposed to play a major role in diabetic cardiomyopathy at least in part by increasing oxidative stress. Further evidence suggests that PKC positively regulates RhoA expression through induction of inducible nitric oxide synthase (iNOS) in diabetes. However, in preliminary studies, we found that inhibition of ROCK itself reduced RhoA expression in diabetic hearts. We hypothesized that there is an interaction between RhoA/ROCK and PKCβ(2) in the form of a positive feedback loop that sustains their activation and the production of reactive oxygen species (ROS). This was investigated in cardiomyocytes isolated from diabetic and control rat hearts, incubated with or without cytochalasin D or inhibitors of ROCK, RhoA, PKCβ(2), or iNOS. Inhibition of RhoA and ROCK markedly attenuated the diabetes-induced increases in PKCβ(2) activity and iNOS and RhoA expression in diabetic cardiomyocytes, while having no effect in control cells. Inhibition of PKCβ(2) and iNOS also normalized RhoA expression and ROCK overactivation, whereas iNOS inhibition reversed the increase in PKCβ(2) activity. Each of these treatments also normalized the diabetes-induced increase in production of ROS. Actin cytoskeleton disruption attenuated the increased expression and/or activity of all of these targets in diabetic cardiomyocytes. These data suggest that, in the diabetic heart, the RhoA/ROCK pathway contributes to contractile dysfunction at least in part by sustaining PKCβ(2) activation and ROS production via a positive feedback loop that requires an intact cytoskeleton.

Indexed as

Actin CytoskeletonAnimalsCells, CulturedDiabetes Mellitus, ExperimentalDiabetic CardiomyopathiesEnzyme InhibitorsFeedback, PhysiologicalGlucoseMaleMyocardial ContractionMyocytes, CardiacNitric Oxide Synthase Type IIOxidative StressPhosphorylationProtein Kinase CProtein Kinase C betaEnzyme InhibitorsGlucoseNitric Oxide Synthase Type IINos2 protein, ratProtein Kinase CProtein Kinase C betaReactive Oxygen SpeciesrhoA GTP-Binding Proteinrho-Associated Kinases

Identifiers

PMID22865386
PMCPMC3469644
OpenAlexW2145045034

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.