Lactate promotes endothelial-to-mesenchymal transition via Snail1 lactylation after myocardial infarction Article Swipe
Min Fan
,
Kun Yang
,
Xiaohui Wang
,
Linjian Chen
,
Parkash S. Gill
,
Tuanzhu Ha
,
Li Liu
,
Nicole Lewis
,
David L. Williams
,
Chuanfu Li
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1126/sciadv.adc9465
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1126/sciadv.adc9465
High levels of lactate are positively associated with the prognosis and mortality in patients with heart attack. Endothelial-to-mesenchymal transition (EndoMT) plays an important role in cardiac fibrosis. Here, we report that lactate exerts a previously unknown function that increases cardiac fibrosis and exacerbates cardiac dysfunction by promoting EndoMT following myocardial infarction (MI). Treatment of endothelial cells with lactate disrupts endothelial cell function and induces mesenchymal-like function following hypoxia by activating the TGF-β/Smad2 pathway. Mechanistically, lactate induces an association between CBP/p300 and Snail1, leading to lactylation of Snail1, a TGF-β transcription factor, through lactate transporter monocarboxylate transporter (MCT)–dependent signaling. Inhibiting Snail1 diminishes lactate-induced EndoMT and TGF-β/Smad2 activation after hypoxia/MI. The MCT inhibitor CHC mitigates lactate-induced EndoMT and Snail1 lactylation. Silence of MCT1 compromises lactate-promoted cardiac dysfunction and EndoMT after MI. We conclude that lactate acts as an important molecule that up-regulates cardiac EndoMT after MI via induction of Snail1 lactylation.
Related Topics
Concepts
Cardiac function curve
Myocardial infarction
Cardiac fibrosis
Mesenchymal stem cell
Hypoxia (environmental)
Lactate dehydrogenase
Fibrosis
Monocarboxylate transporter
Internal medicine
Cardiology
Transporter
Heart failure
Biology
Chemistry
Cell biology
Medicine
Biochemistry
Gene
Enzyme
Organic chemistry
Oxygen
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1126/sciadv.adc9465
- https://www.science.org/doi/pdf/10.1126/sciadv.adc9465?download=true
- OA Status
- gold
- Cited By
- 286
- References
- 66
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4319069454
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4319069454Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1126/sciadv.adc9465Digital Object Identifier
- Title
-
Lactate promotes endothelial-to-mesenchymal transition via Snail1 lactylation after myocardial infarctionWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-02-03Full publication date if available
- Authors
-
Min Fan, Kun Yang, Xiaohui Wang, Linjian Chen, Parkash S. Gill, Tuanzhu Ha, Li Liu, Nicole Lewis, David L. Williams, Chuanfu LiList of authors in order
- Landing page
-
https://doi.org/10.1126/sciadv.adc9465Publisher landing page
- PDF URL
-
https://www.science.org/doi/pdf/10.1126/sciadv.adc9465?download=trueDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.science.org/doi/pdf/10.1126/sciadv.adc9465?download=trueDirect OA link when available
- Concepts
-
Cardiac function curve, Myocardial infarction, Cardiac fibrosis, Mesenchymal stem cell, Hypoxia (environmental), Lactate dehydrogenase, Fibrosis, Monocarboxylate transporter, Internal medicine, Cardiology, Transporter, Heart failure, Biology, Chemistry, Cell biology, Medicine, Biochemistry, Gene, Enzyme, Organic chemistry, OxygenTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
286Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 158, 2024: 97, 2023: 30, 2012: 1Per-year citation counts (last 5 years)
- References (count)
-
66Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.Snail1 | 99, 116, 147 |
| abstract_inverted_index.TGF-β | 88 |
| abstract_inverted_index.exerts | 32 |
| abstract_inverted_index.levels | 1 |
| abstract_inverted_index.report | 29 |
| abstract_inverted_index.Silence | 118 |
| abstract_inverted_index.Snail1, | 81, 86 |
| abstract_inverted_index.attack. | 16 |
| abstract_inverted_index.between | 78 |
| abstract_inverted_index.cardiac | 25, 39, 43, 123, 140 |
| abstract_inverted_index.factor, | 90 |
| abstract_inverted_index.hypoxia | 67 |
| abstract_inverted_index.induces | 63, 75 |
| abstract_inverted_index.lactate | 3, 31, 57, 74, 92, 132 |
| abstract_inverted_index.leading | 82 |
| abstract_inverted_index.through | 91 |
| abstract_inverted_index.unknown | 35 |
| abstract_inverted_index.(EndoMT) | 19 |
| abstract_inverted_index.CBP/p300 | 79 |
| abstract_inverted_index.conclude | 130 |
| abstract_inverted_index.disrupts | 58 |
| abstract_inverted_index.fibrosis | 40 |
| abstract_inverted_index.function | 36, 61, 65 |
| abstract_inverted_index.molecule | 137 |
| abstract_inverted_index.pathway. | 72 |
| abstract_inverted_index.patients | 13 |
| abstract_inverted_index.Treatment | 52 |
| abstract_inverted_index.fibrosis. | 26 |
| abstract_inverted_index.following | 48, 66 |
| abstract_inverted_index.important | 22, 136 |
| abstract_inverted_index.increases | 38 |
| abstract_inverted_index.induction | 145 |
| abstract_inverted_index.inhibitor | 110 |
| abstract_inverted_index.mitigates | 112 |
| abstract_inverted_index.mortality | 11 |
| abstract_inverted_index.prognosis | 9 |
| abstract_inverted_index.promoting | 46 |
| abstract_inverted_index.Inhibiting | 98 |
| abstract_inverted_index.activating | 69 |
| abstract_inverted_index.activation | 105 |
| abstract_inverted_index.associated | 6 |
| abstract_inverted_index.diminishes | 100 |
| abstract_inverted_index.infarction | 50 |
| abstract_inverted_index.myocardial | 49 |
| abstract_inverted_index.positively | 5 |
| abstract_inverted_index.previously | 34 |
| abstract_inverted_index.signaling. | 97 |
| abstract_inverted_index.transition | 18 |
| abstract_inverted_index.association | 77 |
| abstract_inverted_index.compromises | 121 |
| abstract_inverted_index.dysfunction | 44, 124 |
| abstract_inverted_index.endothelial | 54, 59 |
| abstract_inverted_index.exacerbates | 42 |
| abstract_inverted_index.hypoxia/MI. | 107 |
| abstract_inverted_index.lactylation | 84 |
| abstract_inverted_index.transporter | 93, 95 |
| abstract_inverted_index.TGF-β/Smad2 | 71, 104 |
| abstract_inverted_index.lactylation. | 117, 148 |
| abstract_inverted_index.up-regulates | 139 |
| abstract_inverted_index.transcription | 89 |
| abstract_inverted_index.lactate-induced | 101, 113 |
| abstract_inverted_index.monocarboxylate | 94 |
| abstract_inverted_index.Mechanistically, | 73 |
| abstract_inverted_index.lactate-promoted | 122 |
| abstract_inverted_index.mesenchymal-like | 64 |
| abstract_inverted_index.(MCT)–dependent | 96 |
| abstract_inverted_index.Endothelial-to-mesenchymal | 17 |
| cited_by_percentile_year.max | 100 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5087509298, https://openalex.org/A5109518238, https://openalex.org/A5086621430 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 10 |
| corresponding_institution_ids | https://openalex.org/I119443389 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8700000047683716 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.999568 |
| citation_normalized_percentile.is_in_top_1_percent | True |
| citation_normalized_percentile.is_in_top_10_percent | True |