Evidence map›Paper›PMID 37587410›Full record

ArticleCellular & molecular biology letters2023

MiR-15b-5p and PCSK9 inhibition reduces lipopolysaccharide-induced endothelial dysfunction by targeting SIRT4.

Elisa Martino, Nunzia D'Onofrio, Anna Balestrieri, Luigi Mele, Celestino Sardu, Raffaele Marfella, Giuseppe Campanile, Maria Luisa Balestrieri

Open access · goldAbstract read
In one paragraph

Article in Cellular & molecular biology letters, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

24 citing papers in PubMed, 32 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

8 authors at 3 institutions in 1 country.

Elisa MartinoDepartment of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138, Naples, Italy.
Nunzia D'OnofrioDepartment of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138, Naples, Italy. nunzia.donofrio@unicampania.it.ORCID http://orcid.org/0000-0002-5300-9530
Anna BalestrieriFood Safety Department, Istituto Zooprofilattico Sperimentale del Mezzogiorno, Via Salute 2, 80055, Portici, Italy.
Luigi MeleDepartment of Experimental Medicine, University of Campania Luigi Vanvitelli, Via Luciano Armanni 5, 80138, Naples, Italy.
Celestino SarduDepartment of Advanced Clinical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Miraglia, 80138, Naples, Italy.
Raffaele MarfellaDepartment of Advanced Clinical and Surgical Sciences, University of Campania Luigi Vanvitelli, Piazza Miraglia, 80138, Naples, Italy.
Giuseppe CampanileDepartment of Veterinary Medicine and Animal Production, University of Naples Federico II, Via F. Delpino 1, 80137, Naples, Italy.
Maria Luisa BalestrieriDepartment of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138, Naples, Italy.
University of Campania "Luigi Vanvitelli" · ITIstituto Zooprofilattico Sperimentale del Mezzogiorno · ITUniversity of Naples Federico II · IT

Funding

PON I&C 2014-2020-CAPSULE F/200016/01-03/X45STUPORANIMA IZS ME 09/22 RC
6 · The paper itself

Abstract

backgroundEndothelial dysfunction and deregulated microRNAs (miRNAs) participate in the development of sepsis and are associated with septic organ failure and death. Here, we explored the role of miR-15b-5p on inflammatory pathways in lipopolysaccharide (LPS)-treated human endothelial cells, HUVEC and TeloHAEC.

methodsThe miR-15b-5p levels were evaluated in LPS-stimulated HUVEC and TeloHAEC cells by quantitative real-time PCR (qRT-PCR). Functional experiments using cell counting kit-8 (CCK-8), transfection with antagomir, and enzyme-linked immunosorbent assays (ELISA) were conducted, along with investigation of pyroptosis, apoptosis, autophagy, and mitochondrial reactive oxygen species (ROS) by cytofluorometric analysis and verified by fluorescence microscopy. Sirtuin 4 (SIRT4) levels were detected by ELISA and immunoblotting, while proprotein convertase subtilisin-kexin type 9 (PCSK9) expression was determined by flow cytometry (FACS) and immunofluorescence analyses. Dual-luciferase reporter evaluation was performed to confirm the miR-15b-5p-SIRT4 interaction.

resultsThe results showed a correlation among miR-15b-5p, PCSK9, and SIRT4 levels in septic HUVEC and TeloHAEC. Inhibition of miR-15b-5p upregulated SIRT4 content, alleviated sepsis-related inflammatory pathways, attenuated mitochondrial stress, and prevented apoptosis, pyroptosis, and autophagic mechanisms. Finally, a PCSK9 inhibitor (i-PCSK9) was used to analyze the involvement of PCSK9 in septic endothelial injury. i-PCSK9 treatment increased SIRT4 protein levels, opposed the septic inflammatory cascade leading to pyroptosis and autophagy, and strengthened the protective role of miR-15b-5p inhibition. Increased luciferase signal validated the miR-15b-5p-SIRT4 binding.

conclusionsOur in vitro findings suggested the miR-15b-5p-SIRT4 axis as a suitable target for LPS-induced inflammatory pathways occurring in sepsis, and provide additional knowledge on the beneficial effect of i-PCSK9 in preventing vascular damage by targeting SIRT4.

Indexed as

Endothelial CellsMicroRNAsProprotein Convertase 9SirtuinsAntagomirsHumansLipopolysaccharidesMitochondrial ProteinsAntagomirsLipopolysaccharidesMicroRNAsMIRN15 microRNA, humanMitochondrial ProteinsPCSK9 protein, humanProprotein Convertase 9SIRT4 protein, humanSirtuinsAutophagyEndothelial inflammationmicroRNA-15b-5pPCSK9PyroptosisSepsisSIRT4

Identifiers

PMID37587410
PMCPMC10428548
OpenAlexW4385876549

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.