Evidence map›Paper›PMID 40959482›Full record

ArticleMedical research archives2022

Effects of Empagliflozin on Intermittent Hypoxia-Induced TRAF3IP2-Dependent Human Aortic Smooth Muscle Cell Proliferation.

Ryan Dashek, Yusuke Higashi, Nitin A Das, Jacob J Russell, Luis A Martinez-Lemus, R Scott Rector, Bysani Chandrasekar

Abstract read
In one paragraph

Article in Medical research archives, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Trial
  2. Article
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

7 authors.

Ryan DashekComparative Medicine Program, Veterinary Pathobiology, University of Missouri-Columbia, MO, USA.
Yusuke HigashiMedicine, Tulane University School of Medicine, New Orleans, LA, USA.
Nitin A DasCardiothoracic Surgery, UT Health, San Antonio, TX, USA.
Jacob J RussellComparative Medicine Program, Veterinary Pathobiology, University of Missouri-Columbia, MO, USA.
Luis A Martinez-LemusDepartment of Biomedical, Biological and Chemical Engineering, University of Missouri-Columbia, MO, USA.
R Scott RectorResearch Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA.
Bysani ChandrasekarResearch Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA.

Funding

Postdoctoral Training in Comparative MedicineT32OD011126 · OD · UNIVERSITY OF MISSOURI-COLUMBIA · PI Elizabeth C Bryda, Aaron Ericsson · 2012 to 2026
$3.4M
Mechanisms of Microvascular Remodeling ProgressionR01HL088105 · NHLBI · UNIVERSITY OF MISSOURI-COLUMBIA · PI MARTINEZ-LEMUS, LUIS A · 2009 to 2019
$3.3M
BLRD VA I01 BX003271BLRD VA I01 BX005845BLRD VA IK6 BX004016NHLBI NIH HHS R01 HL088105NIH HHS T32 OD011126
6 · The paper itself

Abstract

Aims: Chronic intermittent hypoxia (IH), a characteristic feature of obstructive sleep apnea (OSA), contributes to cardiovascular diseases, including atherosclerosis, potentially through persistent oxidative stress and inflammation. TRAF3IP2 (TRAF3 Interacting Protein 2) is an oxidative stress-responsive proinflammatory adapter molecule and plays a causal role in a preclinical model of atherosclerosis. Since SGLT2 (Sodium/Glucose Cotransporter 2) inhibitors have shown protective effects in CVD by inhibiting oxidative stress and inflammation, we hypothesized that IH promotes the crosstalk between oxidative stress and TRAF3IP2, resulting in IL-6-dependent human aortic smooth muscle cell (SMC) proliferation, and that these effects are inhibited by the SGLT2 inhibitor empagliflozin. Materials and methods: Primary human aortic SMC were exposed to various cycles of IH. Normoxia served as a control. To understand the molecular mechanisms underlying IH-induced nitroxidative stress, TRAF3IP2 and IL-6 induction, and SMC proliferation and those targeted by empagliflozin were determined by treating SMC with various pharmacological inhibitors and viral vectors. Results: IH upregulated TRAF3IP2 expression, TRAF3IP2-dependent superoxide, hydrogen peroxide and nitric oxide generation, NF-κB and HIF-1α activation, IL-6 induction, and SMC proliferation. Exposure to IL-6 by itself induced SMC proliferation in part via TRAF3IP2, IL-6R, gp130, JAK, and STAT3. Further, SMC express SGLT2 at basal conditions, and is upregulated by both IH and IL-6. Importantly, empagliflozin inhibited IH-induced TRAF3IP2 upregulation, reactive oxygen and nitrogen species generation, TRAF3IP2-dependent HIF-1α and NF-κB activation, IL-6 induction, and IL-6-dependent JAK-STAT3-mediated SMC proliferation. Moreover, empagliflozin inhibited IL-6-induced STAT3-dependent SMC proliferation. Conclusions: These results suggest the therapeutic potential of empagliflozin in IH and inflammatory vascular proliferative diseases associated with OSA.

Indexed as

inflammationintermittent hypoxianitric oxideoxidative stressSGLT2

Identifiers

PMID40959482
PMCPMC12435077

What Socratic holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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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 Socratic graph.