Evidence map›Paper›PMID 38112268›Full record

ArticleJournal of diabetes2024

Pravastatin promotes type 2 diabetes vascular calcification through activating intestinal Bacteroides fragilis to induce macrophage M1 polarization.

Cong Chen, Zheng-Feng Liang, Yu-Qi He, An-Qi Li, Yan Gao, Qun-Wen Pan, Jing-Song Cao

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

Article in Journal of diabetes, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

5 citing papers in PubMed, 6 citations in OpenAlex.

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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

7 authors at 2 institutions in 1 country.

Cong ChenThe First Affiliated Hospital, Department of Laboratory Medicine, Hengyang Medical School, University of South China, Hengyang, China.
Zheng-Feng LiangThe First Affiliated Hospital, Institute of Endocrinology and metabolism, Center for Clinical Research in Diabetes, Hengyang Medical School, University of South China, Hengyang, China.
Yu-Qi HeThe First Affiliated Hospital, Department of Laboratory Medicine, Hengyang Medical School, University of South China, Hengyang, China.
An-Qi LiThe First Affiliated Hospital, Institute of Endocrinology and metabolism, Center for Clinical Research in Diabetes, Hengyang Medical School, University of South China, Hengyang, China.
Yan GaoThe First Affiliated Hospital, Institute of Endocrinology and metabolism, Center for Clinical Research in Diabetes, Hengyang Medical School, University of South China, Hengyang, China.
Qun-Wen PanGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Jing-Song CaoThe First Affiliated Hospital, Institute of Endocrinology and metabolism, Center for Clinical Research in Diabetes, Hengyang Medical School, University of South China, Hengyang, China.ORCID https://orcid.org/0000-0002-0133-282X
First Affiliated Hospital of University of South China · CNGuangdong Medical College · CN

Funding

Natural Science Foundation of Hunan Province, China 2021JJ40490Natural Science Foundation of Hunan Province, China 2021JJ70113The Research Foundation of Education Bureau of Hunan Province, China 22A0292
6 · The paper itself

Abstract

backgroundPravastatin is an oral lipid-lowering drug, commonly used by patients with diabetes that is positively correlated with the occurrence of vascular calcification (VC), but the mechanism is unclear.

methodsIn this study, 16S rRNA sequencing and qRT-PCR wereused to detect the differential gut bacteria. Metabolomics and ELISA were used to analyze the differential metabolites. qRT-PCR and western blotting (WB) were used to detect genes expression. Flow cytometry was used to analyze macrophage phenotype. Immunohistochemistry was used to analyze aortic calcification.

resultsWe found that gut Bacteroides fragilis (BF) increased significantly in patients who took pravastatin or type 2 diabetes (T2D) mice treated with pravastatin. In vitro experiments showed that pravastatin had little effect on BF but significantly promoted BF proliferation in vivo. Further analysis showed that ArsR was an important gene for pravastatin to regulate the activation of BF, and overexpression of ArsR significantly promoted the secretion of 3,4,5-trimethoxycinnamic acid (TMCA). Importantly, pravastatin significantly promoted BF secretion of TMCA and significantly increased TMCA secretion in T2D patients or T2D mice. TMCA had little effect on vascular smooth muscle cell calcification but significantly promoted macrophage M1 polarization, which we had demonstrated that M1 macrophages promoted T2D VC. In vivo studies found that pravastatin significantly upregulated TMCA levels in the feces and serum of T2D mice transplanted with BF and promoted the macrophage M1 polarization in bone marrow and the osteoblastic differentiation of aortic cells. Similar results were obtained in T2D mice after intravenous infusion of TMCA.

conclusionsPromoting intestinal BF to secrete TMCA, which leads to macrophage M1 polarization, is an important mechanism by which pravastatin promotes calcification, and the result will be used for the optimization of clinical medication strategies of pravastatin supplying a theoretical basis and experimental basis.

Indexed as

Bacteroides fragilisDiabetes Mellitus, Type 2MacrophagesPravastatinVascular CalcificationAnimalsFemaleGastrointestinal MicrobiomeHumansHydroxymethylglutaryl-CoA Reductase InhibitorsMaleMiceMice, Inbred C57BLHydroxymethylglutaryl-CoA Reductase InhibitorsPravastatinBacteroides fragilismacrophagepravastatintype 2 diabetesvascular calcification

Identifiers

PMID38112268
PMCPMC11128749
OpenAlexW4389950895

What OpenQuestion holds

Texttitle and abstract
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 OpenQuestion graph.