Evidence map›Paper›PMID 40724868›Full record

ArticleInternational journal of molecular sciences2025

PCSK9 Inhibitor Inclisiran Attenuates Cardiotoxicity Induced by Sequential Anthracycline and Trastuzumab Exposure via NLRP3 and MyD88 Pathway Inhibition.

Vincenzo Quagliariello, Massimiliano Berretta, Irma Bisceglia, Martina Iovine, Matteo Barbato, Raffaele Arianna, Maria Laura Canale, Andrea Paccone, Alessandro Inno, Marino Scherillo and 8 more

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Signaling pathways and potential therapeutic agents in trastuzumab-induced cardiotoxicity.Apoptosis : an international journal on programmed cell death · 2026
    Review
  5. Review
  6. Review
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

18 authors.

Vincenzo QuagliarielloDivision of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy.
Massimiliano BerrettaDepartment of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.ORCID 0000-0002-9837-9148
Irma BiscegliaServizi Cardiologici Integrati, Dipartimento Cardio-Toraco-Vascolare, Azienda Ospedaliera San Camillo Forlanini, 00152 Roma, Italy.ORCID 0000-0002-0689-0695
Martina IovineDivision of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy.ORCID 0000-0001-5871-4098
Matteo BarbatoDivision of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy.
Raffaele AriannaDivision of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy.
Maria Laura CanaleU.O.C. Cardiologia, Ospedale Versilia, 55041 Lido di Camaiore, Italy.
Andrea PacconeDivision of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy.
Alessandro InnoMedical Oncology, IRCCS Ospedale Sacro Cuore Don Calabria, 37024 Negrar di Valpolicella, Italy.ORCID 0000-0001-6331-6908
Marino ScherilloCardiologia Interventistica e UTIC, A.O. San Pio, Presidio Ospedaliero Gaetano Rummo, 82100 Benevento, Italy.
Stefano OlivaCardio-Oncology Unit, IRCCS Istituto Tumori, "Giovanni Paolo II", 70124 Bari, Italy.
Christian Cadeddu DessalviDepartment of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy.ORCID 0000-0002-2823-1797
Alfredo MaurielloDivision of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy.ORCID 0000-0001-7060-6938
Carlo MaureaUOC Neurology-Stroke Unit, AORN Cardarelli, 80131 Naples, Italy.
Celeste FondericoDivision of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy.ORCID 0009-0006-5648-4552
Anna Chiara MarateaDivision of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy.
Domenico GabrielliUOC Cardiologia, Dipartimento Cardio-Toraco-Vascolare, Azienda Ospedaliera San Camillo Forlanini, Roma-Fondazione per il Tuo Cuore-Heart Care Foundation, 00152 Firenze, Italy.ORCID 0000-0003-3392-0527
Nicola MaureaDivision of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy.ORCID 0000-0003-3704-0092

Funding

Ministero della Salute 5x1000 Project (5XMILLE_2022_17) titled "Inibitori selettivi di PCSK9 e NLRP3 come strategie preventive della cardiotossicità e aterosclerosi indotta da farmaci antitumorali: impatto del tar-geting lipidico ed infiammatorio in Cardio-Oncologia"
6 · The paper itself

Abstract

Cardiotoxicity related to anthracyclines and trastuzumab represents a significant clinical challenge in cancer therapy, often limiting treatment efficacy and patient survival. The underlying mechanisms of cardiotoxicity involve the activation of NLRP3 and the MyD88-dependent signaling pathway. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), such as inclisiran, are known for their lipid-lowering effects, but emerging data indicate that they may also exert pleiotropic benefits beyond cholesterol reduction. This study investigates whether inclisiran can mitigate the cardiotoxic effects of anthracyclines and trastuzumab through reduction of NLRP3 activation and MyD88 signaling, independently of its effects on dyslipidemia. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were exposed to subclinical concentrations of doxorubicin (1 µM) and trastuzumab in sequential therapy (200 nM), alone or in combination with inclisiran (100 nM) for 24 h. After the incubation period, we performed the following tests: determination of cardiomyocytes apoptosis, analysis of intracellular reactive oxygen species, lipid peroxidation products (including malondialdehyde and 4-hydroxynonenal), intracellular mitofusin-2 and Ca

Indexed as

AnthracyclinesCardiotoxicityMyeloid Differentiation Factor 88NLR Family, Pyrin Domain-Containing 3 ProteinPCSK9 InhibitorsTrastuzumabApoptosisDoxorubicinHumansMyocytes, CardiacReactive Oxygen SpeciesSignal TransductionAnthracyclinesDoxorubicinMYD88 protein, humanMyeloid Differentiation Factor 88NLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanPCSK9 InhibitorsReactive Oxygen SpeciesTrastuzumabcancercardio-oncologycardiotoxicityLDLmetabolismNLRP3PCSK9

Identifiers

PMID40724868
PMCPMC12294440

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.