Evidence mapPaperPMID 39088085Full record

ArticleBasic research in cardiology2024

SGLT1 contributes to glucose-mediated exacerbation of ischemia-reperfusion injury in ex vivo rat heart.

Alhanoof Almalki, Sapna Arjun, Idris Harding, Hussain Jasem, Maria Kolatsi-Joannou, Daniyal J Jafree, Gideon Pomeranz, David A Long, Derek M Yellon, Robert M Bell

Abstract read
In one paragraph

Article in Basic research in cardiology, 2024. 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. Article
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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

10 authors.

Alhanoof Almalki *Hatter Cardiovascular Institute, Institute for Cardiovascular Science, University College London, 67 Chenies Mews, London, WC1E 6HX, UK.
Sapna Arjun *Hatter Cardiovascular Institute, Institute for Cardiovascular Science, University College London, 67 Chenies Mews, London, WC1E 6HX, UK.
Idris HardingHatter Cardiovascular Institute, Institute for Cardiovascular Science, University College London, 67 Chenies Mews, London, WC1E 6HX, UK.
Hussain JasemHatter Cardiovascular Institute, Institute for Cardiovascular Science, University College London, 67 Chenies Mews, London, WC1E 6HX, UK.
Maria Kolatsi-JoannouDevelopmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK.
Daniyal J JafreeDevelopmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK.ORCID 0000-0001-8235-0394
Gideon PomeranzDevelopmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK.
David A LongDevelopmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, London, UK.ORCID 0000-0001-6580-3435
Derek M YellonHatter Cardiovascular Institute, Institute for Cardiovascular Science, University College London, 67 Chenies Mews, London, WC1E 6HX, UK.ORCID 0000-0001-7791-9320
Robert M BellHatter Cardiovascular Institute, Institute for Cardiovascular Science, University College London, 67 Chenies Mews, London, WC1E 6HX, UK. Rob.bell@ucl.ac.uk.ORCID 0000-0003-2199-2638

Funding

British Heart Foundation PG/18/10/33550Rosetrees Trust (PhD2020\100012Wellcome TrustWellcome Trust 220895/Z/20/Z
6 · The paper itself

Abstract

Hyperglycaemia is common during acute coronary syndromes (ACS) irrespective of diabetic status and portends excess infarct size and mortality, but the mechanisms underlying this effect are poorly understood. We hypothesized that sodium/glucose linked transporter-1 (SGLT1) might contribute to the effect of high-glucose during ACS and examined this using an ex-vivo rodent heart model of ischaemia-reperfusion injury. Langendorff-perfused rat hearts were subjected to 35 min ischemia and 2 h reperfusion, with variable glucose and reciprocal mannitol given during reperfusion in the presence of pharmacological inhibitors of SGLT1. Myocardial SGLT1 expression was determined in rat by rtPCR, RNAscope and immunohistochemistry, as well as in human by single-cell transcriptomic analysis. High glucose in non-diabetic rat heart exacerbated reperfusion injury, significantly increasing infarct size from 45 ± 3 to 65 ± 4% at 11-22 mmol/L glucose, respectively (p < 0.01), an association absent in diabetic heart (32 ± 1-37 ± 5%, p = NS). Rat heart expressed SGLT1 RNA and protein in vascular endothelium and cardiomyocytes, with similar expression found in human myocardium by single-nucleus RNA-sequencing. Rat SGLT1 expression was significantly reduced in diabetic versus non-diabetic heart (0.608 ± 0.08 compared with 1.116 ± 0.13 probe/nuclei, p < 0.01). Pharmacological inhibitors phlorizin, canagliflozin or mizagliflozoin in non-diabetic heart revealed that blockade of SGLT1 but not SGLT2, abrogated glucose-mediated excess reperfusion injury. Elevated glucose is injurious to the rat heart during reperfusion, exacerbating myocardial infarction in non-diabetic heart, whereas the diabetic heart is resistant to raised glucose, a finding which may be explained by lower myocardial SGLT1 expression. SGLT1 is expressed in vascular endothelium and cardiomyocytes and inhibiting SGLT1 abrogates excess glucose-mediated infarction. These data highlight SGLT1 as a potential clinical translational target to improve morbidity/mortality outcomes in hyperglycemic ACS patients.

Indexed as

GlucoseMyocardial Reperfusion InjurySodium-Glucose Transporter 1AnimalsDisease Models, AnimalHumansHyperglycemiaIsolated Heart PreparationMaleMyocardial InfarctionMyocardiumMyocytes, CardiacRatsRats, Sprague-DawleyGlucoseSLC5A1 protein, humanSlc5a1 protein, ratSodium-Glucose Transporter 1DiabetesHyperglycemiaMyocardial infarctionReperfusion injurySGLT1SGLT2

Identifiers

PMID39088085
PMCPMC11461679

What Socratic holds

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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.