LOX-1 promotes cardiac hypertrophy via p38MAPK signaling in alcoholic cardiomyopathy

Q: What is the clinical evidence from this study?

Population: Alcoholic cardiomyopathy (n=30). Intervention: LOX-1 knockdown (adenoviral shRNA) vs. Ethanol exposure only (ACM group). Primary outcome: Cardiac hypertrophy, apoptosis, and cardiac function (e.g., EF, FS).

Q: What does this research mean for the field?

LOX-1 knockdown ameliorates alcoholic cardiomyopathy by inhibiting p38MAPK-mediated autophagy, effectively suppressing myocardial hypertrophy and apoptosis. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Yifan Zhang; Yue Xu; Na Zhou; Xin Wang; Xiaoyan Lv; Dong Liu; Wenli Zhang; Zhanbin Feng

doi:10.1007/s10238-026-02322-0

September 18, 2026Clinical and Experimental MedicineOpen Access

LOX-1 promotes cardiac hypertrophy via p38MAPK signaling in alcoholic cardiomyopathy

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Key result

LOX-1 knockdown ameliorates alcoholic cardiomyopathy by suppressing p38MAPK-mediated autophagy, hypertrophy, and apoptosis.

n=30

Why the study?

The role of LOX-1/p38MAPK signaling in mediating cardiac hypertrophy in alcoholic cardiomyopathy remains unclear.

Does LOX-1 knockdown prevent cardiac hypertrophy and dysfunction in a rat model of alcoholic cardiomyopathy?

Key Points

To determine the role and molecular mechanism of LOX-1 and downstream p38MAPK signaling in regulating cardiomyocyte hypertrophy, autophagy, and apoptosis in alcoholic cardiomyopathy.
Treated primary neonatal rat ventricular cardiomyocytes (pNRVMs) with ethanol and transfected them with shRNA or overexpression vectors targeting LOX-1 or p38MAPK.
Established an in vivo alcoholic cardiomyopathy model in Sprague-Dawley rats administered ethanol, followed by adenoviral delivery of sh-LOX-1.
Assessed cardiac structure and function via echocardiography, cell morphology by H&E, autophagosomes by TEM, apoptosis by flow cytometry and TUNEL, and molecular markers using RT-qPCR and Western blot.
In pNRVMs, ethanol increased apoptotic cells from ~ 5–8% to ~ 20%, which LOX-1 overexpression elevated to ~ 30% and LOX-1 knockdown reduced to ~ 10–12%; p38MAPK overexpression restored apoptosis to ~ 25–28%.
Ethanol stimulated p-p38MAPK and elevated hypertrophic markers (ANP, BNP, MEF2C, β-MHC) while downregulating α-MHC; these alterations were reversed by LOX-1 knockdown and partially restored by p38MAPK overexpression.
In rats with alcoholic cardiomyopathy, ethanol markedly reduced ejection fraction to ~ 40% and fractional shortening to ~ 20% while increasing HW/TL, LVM/TL, and serum markers (LDH, cTnI, CK-MB), all of which were alleviated by LOX-1 knockdown.

Structured PICO

Does LOX-1 knockdown prevent cardiac hypertrophy and dysfunction in a rat model of alcoholic cardiomyopathy?

P

Population

30 male adult Sprague-Dawley rats and primary neonatal rat ventricular cardiomyocytes were used to establish in vivo and in vitro models of alcoholic cardiomyopathy.

I

Intervention

In vivo: Adenoviral vectors containing shRNA targeting LOX-1 (1×10⁸ PFU in 100 µL saline via tail vein injection, twice weekly during weeks 13–16) added to a 16-week gradual incremental alcohol adaptation regimen (up to 60% ethanol gavage + 20% ethanol in drinking water). In vitro: shRNA or overexpression constructs targeting LOX-1 or p38MAPK added to ethanol treatment.

C

Comparator

In vivo: Blank group (equal volume of normal saline by gavage and regular drinking water) and ACM group (alcohol adaptation regimen only). In vitro: Blank cells and ethanol-only treated cells.

O

Outcome

Cardiac hypertrophy (assessed by left ventricular mass to tibial length ratio, heart weight to tibial length ratio, cardiomyocyte cross-sectional area, and hypertrophic gene markers ANP, BNP, MEF2C, β-MHC) and cardiac function (EF and FS via echocardiography) at 16 weeks.surrogate

LOX-1 knockdown effectively ameliorates ethanol-induced cardiac hypertrophy and apoptosis by inhibiting p38MAPK-mediated autophagy in a preclinical model of alcoholic cardiomyopathy.

Limitations

The downstream signaling network of LOX-1 may not be limited to the p38MAPK pathway.

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

LOX-1 inhibition merits further preclinical study in alcoholic cardiomyopathy; leaves open translation to human therapy.

Abstract

Cardiac hypertrophy is a hallmark of alcoholic cardiomyopathy (ACM). The role of Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)/p38MAPK in mediating hypertrophy in ACM remains unclear. Primary neonatal rat ventricular cardiomyocytes (pNRVMs) were treated with ethanol and transfected with shRNA or overexpression constructs targeting LOX-1 or p38MAPK to investigate their roles in ethanol-induced cardiomyocyte hypertrophy, autophagy, and apoptosis. Sprague-Dawley rats were administered with ethanol to establish ACM models. H&E staining was used to assess cellular morphology, and transmission electron microscopy was used to detect autophagosomes. Apoptosis was detected by flow cytometry and TUNEL staining. RT‑qPCR and Western blot were used to determine the expression levels of LOX‑1, p38MAPK, and markers related to hypertrophy, autophagy, and apoptosis. Cardiac function parameters were measured by echocardiography. In pNRVMs, alcohol promoted p‑p38MAPK/p38MAPK expression via upregulation of LOX‑1, which inhibited autophagy (elevated Beclin‑1, ATG5, LC3‑II/LC3‑I, LAMP1 and p62) and subsequently promoted cardiomyocyte hypertrophy (upregulated ANP, BNP, MEF2C, and β‑MHC, with downregulated α‑MHC) and apoptosis (increased Bax and cleaved caspase‑3). LOX‑1 overexpression exacerbated these alterations, whereas LOX‑1 knockdown partially reversed them. P38MAPK overexpression partially counteracted the effects conferred by LOX‑1 knockdown. LOX‑1 knockdown similarly enhanced autophay and suppressed hypertrophic and apoptotic markers, improved cardiac function (elevated EF and FS), reduced hypertrophy indices (HW/TL and LVM/TL), and lowered serum injury markers (LDH, cTnI, and CK‑MB) in ACM rats. Histological and TUNEL staining further supported the alleviation of myocardial hypertrophy and apoptosis. LOX-1 knockdown promotes p38MAPK-mediated autophagy, effectively suppressing myocardial hypertrophy and consequent apoptosis, and ultimately ameliorating ACM.

Discussion

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Cite This Study

Zhang et al. (2026) studied Alcoholic cardiomyopathy (n=30). LOX-1 knockdown (adenoviral shRNA) vs. Ethanol exposure only (ACM group) was evaluated on Cardiac hypertrophy, apoptosis, and cardiac function (e.g., EF, FS). LOX-1 knockdown ameliorated alcoholic cardiomyopathy by inhibiting p38MAPK-mediated autophagy, which effectively suppressed myocardial hypertrophy and consequent apoptosis.

synapsesocial.com/papers/6ad0fd1915427f6a8404051f https://doi.org/10.1007/s10238-026-02322-0

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LOX-1 promotes cardiac hypertrophy via p38MAPK signaling in alcoholic cardiomyopathy

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

LOX-1 promotes cardiac hypertrophy via p38MAPK signaling in alcoholic cardiomyopathy

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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