Evidence map›Paper›PMID 34526601›Full record

ArticleScientific reports2021

Empagliflozin maintains capillarization and improves cardiac function in a murine model of left ventricular pressure overload.

Masaaki Nakao, Ippei Shimizu, Goro Katsuumi, Yohko Yoshida, Masayoshi Suda, Yuka Hayashi, Ryutaro Ikegami, Yung Ting Hsiao, Shujiro Okuda, Tomoyoshi Soga and 1 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

31 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Endothelial dysfunction in chronic kidney disease: a clinical perspective.American journal of physiology. Heart and circulatory physiology · 2025
    Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. The Effects of SGLT2 Inhibitors on Blood Pressure and Other Cardiometabolic Risk Factors.International journal of molecular sciences · 2024 · on this map
    Review
  15. Review
  16. SGLT2 Inhibitors and How They Work Beyond the Glucosuric Effect. State of the Art.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024
    Review
  17. Review
  18. Review
  19. Review
  20. 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

11 authors at 4 institutions in 1 country.

Masaaki Nakao *Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
Ippei Shimizu *Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. ippeishimizu@yahoo.co.jp.
Goro KatsuumiDepartment of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Yohko YoshidaDepartment of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Masayoshi SudaDepartment of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
Yuka HayashiDepartment of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
Ryutaro IkegamiDepartment of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
Yung Ting HsiaoDepartment of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Shujiro OkudaDivision of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510, Japan.
Tomoyoshi SogaInstitute for Advanced Biosciences, Keio University, Yamagata, 997-0052, Japan.
Tohru MinaminoDepartment of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. t_minamino@yahoo.co.jp.
Juntendo University · JPNiigata University · JPJapan Agency for Medical Research and Development · JPKeio University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Patients with type 2 diabetes treated with Sodium glucose transporter 2 (SGLT2) inhibitors show reduced mortality and hospitalization for heart failure (HF). SGLT2 inhibitors are considered to activate multiple cardioprotective pathways; however, underlying mechanisms are not fully described. This study aimed to elucidate the underlying mechanisms of the beneficial effects of SGLT2 inhibitors on the failing heart. We generated a left ventricular (LV) pressure overload model in C57BL/6NCrSlc mice by transverse aortic constriction (TAC) and examined the effects of empagliflozin (EMPA) in this model. We conducted metabolome and transcriptome analyses and histological and physiological examinations. EMPA administration ameliorated pressure overload-induced systolic dysfunction. Metabolomic studies showed that EMPA increased citrulline levels in cardiac tissue and reduced levels of arginine, indicating enhanced metabolism from arginine to citrulline and nitric oxide (NO). Transcriptome suggested possible involvement of the insulin/AKT pathway that could activate NO production through phosphorylation of endothelial NO synthase (eNOS). Histological examination of the mice showed capillary rarefaction and endothelial apoptosis after TAC, both of which were significantly improved by EMPA treatment. This improvement was associated with enhanced expression phospho-eNOS and NO production in cardiac endothelial cells. NOS inhibition attenuated these cardioprotective effects of EMPA. The in vitro studies showed that catecholamine-induced endothelial apoptosis was inhibited by NO, arginine, or AKT activator. EMPA activates the AKT/eNOS/NO pathway, which helps to suppress endothelial apoptosis, maintain capillarization and improve systolic dysfunction during LV pressure overload.

Indexed as

AnimalsBenzhydryl CompoundsBiomarkersBlood PressureCardiotonic AgentsDisease ManagementDisease Models, AnimalGene Expression ProfilingGlucosidesHeart FailureImmunohistochemistryMetabolomeMetabolomicsMiceMicrocirculationModels, BiologicalBenzhydryl CompoundsBiomarkersCardiotonic AgentsempagliflozinGlucosidesNorepinephrineSodium-Glucose Transporter 2 Inhibitors

Identifiers

PMID34526601
PMCPMC8443662
OpenAlexW3201065222

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.