Evidence map›Paper›PMID 32264868›Full record

ArticleCardiovascular diabetology2020

Sodium-glucose cotransporter 2 inhibitors antagonize lipotoxicity in human myeloid angiogenic cells and ADP-dependent activation in human platelets: potential relevance to prevention of cardiovascular events.

Valentina Spigoni, Federica Fantuzzi, Cecilia Carubbi, Giulia Pozzi, Elena Masselli, Giuliana Gobbi, Anna Solini, Riccardo C Bonadonna, Alessandra Dei Cas

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular diabetology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
6.5field-weighted citation impact, top 2% 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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

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  20. SGLT2 Inhibitors in Aging-Related Cardiovascular Disease: A Review of Potential Mechanisms.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2023
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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

9 authors at 3 institutions in 1 country.

Valentina SpigoniEndocrinology and Metabolism, Department of Medicine and Surgery, University of Parma, Parma, Italy.
Federica FantuzziEndocrinology and Metabolism, Department of Medicine and Surgery, University of Parma, Parma, Italy.
Cecilia CarubbiDepartment of Medicine and Surgery, Unit of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), University of Parma, Parma, Italy.
Giulia PozziDepartment of Medicine and Surgery, Unit of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), University of Parma, Parma, Italy.
Elena MasselliDepartment of Medicine and Surgery, Unit of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), University of Parma, Parma, Italy.
Giuliana GobbiDepartment of Medicine and Surgery, Unit of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), University of Parma, Parma, Italy.
Anna SoliniDepartment of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy.
Riccardo C BonadonnaEndocrinology and Metabolism, Department of Medicine and Surgery, University of Parma, Parma, Italy. riccardo.bonadonna@unipr.it.
Alessandra Dei CasEndocrinology and Metabolism, Department of Medicine and Surgery, University of Parma, Parma, Italy.
University of Parma · ITOspedale di Parma · ITUniversity of Pisa · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe clear evidence of cardiovascular benefits in cardiovascular outcome trials of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in type 2 diabetes might suggest an effect on atherosclerotic plaque vulnerability and/or thrombosis, in which myeloid angiogenic cells (MAC) and platelets (PLT) are implicated. We tested the effects of SGLT2i on inflammation and oxidant stress in a model of stearic acid (SA)-induced lipotoxicity in MAC and on PLT activation. The possible involvement of the Na

methodMAC and PLT were isolated from peripheral blood of healthy subjects and incubated with/without SGLT2i [empagliflozin (EMPA) and dapagliflozin (DAPA) 1-100 μM] to assess their effects on SA (100 μM)-induced readouts of inflammation, oxidant stress and apoptosis in MAC and on expression of PLT activation markers by flow-cytometry after ADP-stimulation. Potential NHE involvement was tested with amiloride (aspecific NHE inhibitor) or cariporide (NHE1 inhibitor). Differences among culture conditions were identified using one-way ANOVA or Friedman test.

resultsNHE isoforms (1,5-9), but not SGLT2 expression, were expressed in MAC and PLT. EMPA and DAPA (100 μM) significantly reduced SA-induced inflammation (IL1β, TNFα, MCP1), oxidant stress (SOD2, TXN, HO1), but not apoptosis in MAC. EMPA and DAPA (both 1 μM) reduced PLT activation (CD62p and PAC1 expression). SGLT2i effects were mimicked by amiloride, and only partially by cariporide, in MAC, and by both inhibitors in PLT.

conclusionsEMPA and DAPA ameliorated lipotoxic damage in stearate-treated MAC, and reduced ADP-stimulated PLT activation, potentially via NHE-inhibition, thereby pointing to plaque stabilization and/or thrombosis inhibition as potential mechanism(s) involved in SGLT2i-mediated cardiovascular protection.

Indexed as

Adenosine DiphosphateApoptosisBenzhydryl CompoundsBlood PlateletsCells, CulturedEndothelial Progenitor CellsGlucosidesHumansInflammation MediatorsOxidative StressPlatelet ActivationSignal TransductionSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsSodium-Hydrogen ExchangersStearic AcidsAdenosine DiphosphateBenzhydryl CompoundsdapagliflozinempagliflozinGlucosidesInflammation MediatorsSLC5A2 protein, humanSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsSodium-Hydrogen Exchangersstearic acidStearic AcidsAtherosclerosisMyeloid angiogenic cellsPlateletsSGLT-2 inhibitorsSodium-proton exchanger

Identifiers

PMID32264868
PMCPMC7140327
OpenAlexW3015053160

What OpenQuestion holds

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LicenceCC BY
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 OpenQuestion graph.