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AAV2/8-hSMAD3 gene delivery attenuates aortic atherogenesis, enhances Th2 response without fibrosis, in LDLR-KO mice on high cholesterol diet

Overview of attention for article published in Journal of Translational Medicine, September 2014
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (88th percentile)

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1 news outlet
twitter
1 tweeter
patent
2 patents

Citations

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7 Dimensions

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13 Mendeley
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Title
AAV2/8-hSMAD3 gene delivery attenuates aortic atherogenesis, enhances Th2 response without fibrosis, in LDLR-KO mice on high cholesterol diet
Published in
Journal of Translational Medicine, September 2014
DOI 10.1186/s12967-014-0252-8
Pubmed ID
Authors

Hongqing Zhu, Maohua Cao, Jose A Figueroa, Everado Cobos, Barry F Uretsky, Maurizio Chiriva-Internati, Paul L Hermonat

Abstract

BackgroundInflammation is a key etiologic component in atherogenesis and transforming growth factor beta 1 (TGFß1) is a well known anti-inflammatory cytokine which potentially might be used to limit it. Yet TGFß1 is pleiomorphic, causing fibrosis, cell taxis, and under certain circumstances, can even worsen inflammation. SMAD3 is an important member of TGFß1¿s signal transduction pathway, but is a fully intracellular protein.ObjectivesWith the hope of attenuating TGFß1¿s adverse systemic effects (eg. fibrosis) and accentuating its anti-inflammatory activity, we proposed the use of human (h)SMAD3 as an intracellular substitute for TGFß1.Study designTo test this hypothesis adeno-associated virus type 2/8 (AAV)/hSMAD3 or AAV/Neo (control) was tail vein injected into the low density lipoprotein receptor knockout (LDLR-KO) mice, then placed on a high-cholesterol diet (HCD).ResultsThe hSMAD3 delivery was associated with significantly lower atherogenesis as measured by larger aortic cross sectional area, thinner aortic wall thickness, and lower aortic systolic blood velocity compared with Neo gene-treated controls. HSMAD3 delivery also resulted in fewer aortic macrophages by immunohistochemistry for CD68 and ITGAM, and quantitative reverse transcriptase polymerase chain reaction analysis of EMR and ITGAM. Overall, aortic cytokine expression showed an enhancement of Th2 response (higher IL-4 and IL-10); while Th1 response (IL-12) was lower with hSMAD3 delivery. While TGFß1 is often associated with increased fibrosis, AAV/hSMAD3 delivery exhibited no increase of collagen 1A2 or significantly lower 2A1 expression in the aorta compared with Neo-delivery. Connective tissue growth factor (CTGF), a mediator of TGFß1/SMAD3-induced fibrosis, was unchanged in hSMAD3-delivered aortas. In the liver, all three of these genes were down-regulated by hSMAD3 gene delivery.ConclusionThese data strongly suggest that AAV/hSMAD3 delivery gave anti-atherosclerosis therapeutic effect without the expected undesirable effect of TGFß1-associated fibrosis.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 13 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 4 31%
Student > Ph. D. Student 2 15%
Student > Doctoral Student 1 8%
Student > Bachelor 1 8%
Other 1 8%
Other 3 23%
Unknown 1 8%
Readers by discipline Count As %
Medicine and Dentistry 5 38%
Agricultural and Biological Sciences 2 15%
Immunology and Microbiology 1 8%
Biochemistry, Genetics and Molecular Biology 1 8%
Psychology 1 8%
Other 1 8%
Unknown 2 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 13. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 March 2022.
All research outputs
#2,216,453
of 21,322,016 outputs
Outputs from Journal of Translational Medicine
#345
of 3,686 outputs
Outputs of similar age
#25,610
of 223,437 outputs
Outputs of similar age from Journal of Translational Medicine
#1
of 1 outputs
Altmetric has tracked 21,322,016 research outputs across all sources so far. Compared to these this one has done well and is in the 89th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,686 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.0. This one has done particularly well, scoring higher than 90% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 223,437 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 88% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them