Evidence map›Paper›PMID 42686971›Full record

ArticleGeroScience2026

PCSK9 inhibition attenuates alcohol-induced cardiovascular dysfunction and links hepatic lipid accumulation to impaired myocardial contractile reserve.

Csaba Matyas, Eszter Trojnar, Partha Mukhopadhyay, Suxian Zhao, Burhan Yokus, Bruno Paes-Leme, Yohannes Getiye, Falk W Lohoff, György Haskó, Pal Pacher

Abstract read
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In one paragraph

Article in GeroScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Csaba MatyasLaboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 2N-17, Rockville, MD, 20852, USA.
Eszter TrojnarLaboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 2N-17, Rockville, MD, 20852, USA.
Partha MukhopadhyayLaboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 2N-17, Rockville, MD, 20852, USA.
Suxian ZhaoLaboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 2N-17, Rockville, MD, 20852, USA.
Burhan YokusLaboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 2N-17, Rockville, MD, 20852, USA.
Bruno Paes-LemeLaboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 2N-17, Rockville, MD, 20852, USA.
Yohannes GetiyeLaboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 2N-17, Rockville, MD, 20852, USA.
Falk W LohoffSection On Clinical Genomics and Experimental Therapeutics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
György HaskóDepartment of Anesthesiology, Columbia University, New York, NY, USA.
Pal PacherLaboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 2N-17, Rockville, MD, 20852, USA. pacher@mail.nih.gov.ORCID http://orcid.org/0000-0001-7036-8108

Funding

NIAAA NIH HHS 1ZIAAA000375-20
6 · The paper itself

Abstract

Excessive alcohol consumption accelerates cardiovascular aging by promoting oxidative stress, inflammation, lipid dysregulation, fibrotic remodeling, and loss of ventricular-vascular reserve. PCSK9, a key regulator of cholesterol metabolism, has emerged as a mediator of age-related cardiovascular dysfunction and alcohol-associated liver and neurovascular injury. We investigated whether PCSK9 inhibition protects against alcohol-induced cardiovascular dysfunction and associated cardiac-hepatic injury in rats. Male Sprague-Dawley rats were assigned to pair-fed control or 35% ethanol liquid diet groups and treated weekly with subcutaneous alirocumab, 50 mg/kg, or vehicle for 6 weeks. Blood alcohol and cholesterol levels were measured; cardiac function was assessed by echocardiography and invasive pressure-volume analysis; and myocardial, vascular, and hepatic injury markers were quantified. Alirocumab reduced total cholesterol in both pair-fed and ethanol-fed rats without altering blood alcohol levels. Chronic ethanol exposure impaired systolic performance, myocardial contractile reserve, diastolic relaxation, and ventricular-arterial coupling, as reflected by reduced stroke volume, cardiac output, ejection fraction, fractional area change, dP/dtmax, stroke work, ESPVR slope, PRSW, and dP/dtmax-EDV, together with abnormalities in TauWeiss and dP/dtmin. PCSK9 inhibition markedly attenuated these functional deficits. Alirocumab also reduced ethanol-induced myocardial and vascular malondialdehyde accumulation and suppressed myocardial induction of NOX4, LOX1, iNOS, TNF-α, ANP, and profibrotic markers. Ethanol increased myocardial fibrosis, hepatic triglyceride accumulation, perilipin-2 staining, and mild hepatic fibrotic remodeling, all of which were attenuated by alirocumab. Liver triglyceride content correlated inversely with ESPVR slope and PRSW. These findings identify PCSK9 as a potential therapeutic target for alcohol-related cardiovascular dysfunction and associated cardiac-hepatic injury.

Indexed as

Accelerated agingAlcoholCardiac functionPCSK9PCSK9 inhibition

Identifiers

PMID42686971

What Socratic holds

Textmetadata
Read underepoch 390

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.