Evidence mapPaperPMID 35426600Full record

ArticleGeroScience2022

SGLT2 inhibition attenuates arterial dysfunction and decreases vascular F-actin content and expression of proteins associated with oxidative stress in aged mice.

Rogerio N Soares, Francisco I Ramirez-Perez, Francisco J Cabral-Amador, Mariana Morales-Quinones, Christopher A Foote, Thaysa Ghiarone, Neekun Sharma, Gavin Power, James A Smith, R Scott Rector and 3 more

Open access · hybridAbstract read
In one paragraph

Article in GeroScience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% 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

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.

  1. Pooled it
  2. ENAC blockade reduces blood pressure and arterial stiffness in adults with obesity and insulin resistance.American journal of physiology. Heart and circulatory physiology · 2026
    Trial
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Sodium-glucose cotransporter 2 inhibitors and atherosclerosis.American journal of preventive cardiology · 2025
    Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Reduced cofilin activity as a mechanism contributing to endothelial cell stiffening in type 2 diabetes.American journal of physiology. Heart and circulatory physiology · 2025
    Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Review
  20. Sitting leg vasculopathy: potential adaptations beyond the endothelium.American journal of physiology. Heart and circulatory physiology · 2024
    Review
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

13 authors at 3 institutions in 1 country.

Rogerio N SoaresDepartment of Medicine, University of Missouri, Columbia, MO, USA.
Francisco I Ramirez-PerezDepartment of Medicine, University of Missouri, Columbia, MO, USA.
Francisco J Cabral-AmadorDepartment of Medicine, University of Missouri, Columbia, MO, USA.
Mariana Morales-QuinonesDepartment of Medicine, University of Missouri, Columbia, MO, USA.
Christopher A FooteDepartment of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, USA.
Thaysa GhiaroneDepartment of Medicine, University of Missouri, Columbia, MO, USA.
Neekun SharmaDepartment of Medicine, University of Missouri, Columbia, MO, USA.
Gavin PowerDepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, USA.
James A SmithDepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, USA.
R Scott RectorDepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, USA.
Luis A Martinez-LemusDepartment of Medicine, University of Missouri, Columbia, MO, USA.
Jaume PadillaDepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO, USA. padillaja@missouri.edu.
Camila Manrique-AcevedoResearch Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO, USA. manriquec@health.missouri.edu.ORCID 0000-0001-9341-404X
University of Missouri · USHarry S. Truman Memorial Veterans' Hospital · USUniversity of Missouri Health System · US

Funding

WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · 2022 to 2025
$5.6M
Hepatic eNOS in the regulation of NASHI01BX003271 · HARRY S. TRUMAN MEMORIAL VA HOSPITAL · 2025 to 2025
BLRD VA I01 BX003271NHLBI NIH HHS R01 HL142770NHLBI NIH HHS R01 HL153264NIDDK NIH HHS P30 DK020579NIH HHS R01 HL142770NIH HHS R01HL1532654
6 · The paper itself

Abstract

Aging of the vasculature is characterized by endothelial dysfunction and arterial stiffening, two key events in the pathogenesis of cardiovascular disease (CVD). Treatment with sodium glucose transporter 2 (SGLT2) inhibitors is now known to decrease cardiovascular morbidity and mortality in type 2 diabetes. However, whether SGLT2 inhibition attenuates vascular aging is unknown. We first confirmed in a cohort of adult subjects that aging is associated with impaired endothelial function and increased arterial stiffness and that these two variables are inversely correlated. Next, we investigated whether SGLT2 inhibition with empagliflozin (Empa) ameliorates endothelial dysfunction and reduces arterial stiffness in aged mice with confirmed vascular dysfunction. Specifically, we assessed mesenteric artery endothelial function and stiffness (via flow-mediated dilation and pressure myography mechanical responses, respectively) and aortic stiffness (in vivo via pulse wave velocity and ex vivo via atomic force microscopy) in Empa-treated (14 mg/kg/day for 6 weeks) and control 80-week-old C57BL/6 J male mice. We report that Empa-treated mice exhibited improved mesenteric endothelial function compared with control, in parallel with reduced mesenteric artery and aortic stiffness. Additionally, Empa-treated mice had greater vascular endothelial nitric oxide synthase activation, lower phosphorylated cofilin, and filamentous actin content, with downregulation of pathways involved in production of reactive oxygen species. Our findings demonstrate that Empa improves endothelial function and reduces arterial stiffness in a preclinical model of aging, making SGLT2 inhibition a potential therapeutic alternative to reduce the progression of CVD in older individuals.

Indexed as

Diabetes Mellitus, Type 2Sodium-Glucose Transporter 2 InhibitorsVascular DiseasesActinsAgedAnimalsHumansMaleMiceMice, Inbred C57BLOxidative StressPulse Wave AnalysisSodium-Glucose Transporter 2ActinsSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsAgingArterial stiffnessEndothelial functionOxidative stressSGLT2

Identifiers

PMID35426600
PMCPMC9213629
OpenAlexW4224082795

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.