Intravenous high mobility group box 1 fragment improves cardiac function, fibrosis, and coronary flow in porcine ischemic cardiomyopathy model

Q: What is the clinical evidence from this study?

Population: Ischemic cardiomyopathy (porcine model) (n=12). Intervention: Intravenous high mobility group box 1 (HMGB1) fragment vs. Normal saline. Primary outcome: Change in left ventricular ejection fraction (ΔLVEF) at 8 weeks (p=0.0015).

Q: What does this research mean for the field?

Intravenous administration of the HMGB1 fragment significantly improves left ventricular ejection fraction, reduces fibrosis, and enhances coronary flow in a porcine model of ischemic cardiomyopathy. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Yoshito Ito; Masashi Kawamura; T Kawamura; Katsuto Tamai; Daisuke Yoshioka; Ryohei Matsuura; Ai Kawamura; Yusuke Misumi; Akima Harada; Tadashi Watabe; Takasumi Goto; Atsushi Yamada; Hisakazu Ogita; Masaki Taira; Kazuo Shimamura; Shigeru Miyagawa

doi:10.1038/s41598-026-38592-7

February 11, 2026Scientific ReportsOpen Access

Intravenous high mobility group box 1 fragment improves cardiac function, fibrosis, and coronary flow in porcine ischemic cardiomyopathy model

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Key result

IV HMGB1 fragment improves LVEF ~11% vs controls in a porcine ischemic cardiomyopathy model.

P=0.0015
n=12

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Why the study?

HMGB1 promotes mobilization of MSCs from bone marrow to contribute to tissue repair, but its therapeutic effect on cardiac function in ischemic cardiomyopathy was unproven.

Does intravenous HMGB1 fragment improve cardiac function, coronary flow, and cardiac fibrosis in a porcine ischemic cardiomyopathy model?

Key Points

To determine whether intravenous administration of high mobility group box 1 (HMGB1) fragment promotes endogenous cardiac repair, reduces fibrosis, and improves myocardial function in a porcine model of ischemic cardiomyopathy.
Twelve swine with ischemic cardiomyopathy induced by an ameroid constrictor placed around the LAD ostium were allocated to either intravenous HMGB1 fragment (N=7, five doses every 48 hours) or saline control (N=5).
Cardiac function, regional strain, myocardial scar size, and coronary hemodynamics were evaluated before treatment and after 8 weeks of follow-up using echocardiography, cMRI with late gadolinium enhancement, 13N-ammonia PET, and coronary pressure wire measurements.
Post-mortem histological analyses (Masson trichrome, HE, CD31 immunohistochemistry) and RT-PCR for reparative factors (SDF1, HGF) were performed on extracted border-zone and remote myocardial tissue.
Echocardiography showed significant improvement in left ventricular ejection fraction (ΔLVEF: +11.0±5.0% vs -4.8±5.8%, p=0.0015) and reduced end-systolic volume (ΔLVESV: -1.0±4.8 ml vs +7.3±2.7 ml, p=0.0043) in the HMGB1 group compared to controls at 8 weeks.
cMRI confirmed a reduction in scarred myocardial area (-11.0±6.8% vs +9.4±4.3%, p=0.0062), and pressure wire studies demonstrated superior increases in average coronary flow reserve (ΔCFR: +0.45 ± 0.27 vs +0.01 ± 0.19, p=0.0166) and resistive reserve ratio (ΔRRR: +0.50 ± 0.25 vs +0.07 ± 0.24, p=0.0176).
Histology revealed significantly smaller cardiomyocyte diameter (26.6 ± 0.8 µm vs 38.0 ± 2.7 μm, p=0.0339) and higher CD31-positive endothelial cell density (1033 ± 249 /mm2 vs 640 ± 57 /mm2, p=0.0339), alongside elevated expression of SDF1 (p=0.0018) and HGF (p=0.0264).

Structured PICO

Does intravenous HMGB1 fragment improve cardiac function, coronary flow, and cardiac fibrosis in a porcine ischemic cardiomyopathy model?

P

Population

12 female Gottingen mini pigs weighing 15-25 kg with ischemic cardiomyopathy (ICM) induced by ameroid constrictor placement around the LAD ostium and LAD ligation.

I

Intervention

High mobility group box 1 (HMGB1) fragment 3 mg/kg administered intravenously for 20-30 minutes, one dose every 48 hours for five doses.

C

Comparator

Same amount of normal saline administered intravenously.

O

Outcome

Change in global cardiac function (left ventricular ejection fraction [LVEF] and left ventricular end-systolic volume [LVESV]) measured by echocardiography and cardiac MRI at 8 weeks after treatment.surrogate

Main Result

Absolute Event Rate: 11% vs -4.8%

p-value: p=0.0015

Intravenous administration of the HMGB1 fragment improved cardiac function, enhanced coronary flow, and reduced fibrosis in a preclinical porcine model of ischemic cardiomyopathy, suggesting its potential as a regenerative therapy for severe heart failure.

Limitations

Direct evidence of mesenchymal stem cell homing to the injured myocardium was not obtained.
Peripheral blood analyses performed immediately before and one day after administration showed substantial inter-individual variability and were therefore not included.
Wheat germ agglutinin staining to evaluate cardiomyocyte size could not be performed due to technical limitations in preparing frozen sections.
Potential off-target effects of HMGB1 fragment administration in other organs were not assessed.

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Implication

Should not change practice; hypothesis-generating for HMGB1 fragment in ischemic cardiomyopathy.

Abstract

One of the regenerative medicine approaches for severe heart failure (HF) involves enhancing the inherent regenerative capacity, with mesenchymal stem cells (MSCs) being a crucial element. High mobility group box 1 (HMGB1) has been reported to promote the mobilization of MSCs from the bone marrow and contribute to tissue repair. We hypothesized that cardiac function would improve through this mechanism in a porcine ischemic cardiomyopathy (ICM) model and analyzed its effectiveness using various imaging modalities, histological analyses, and RT-PCR. Echocardiography revealed an increased left ventricular (LV) ejection fraction and reduced LV end-systolic volume. Cardiac magnetic resonance imaging with late gadolinium enhancement demonstrated improved regional LV strain and a smaller scarred myocardial zone. A pressure wire study in the coronary arteries showed enhanced coronary flow reserve and resistive reserve ratio. Histological analysis exhibited a smaller cardiomyocyte diameter, reduced fibrosis area, and an increased number of CD31-positive endothelial cells. RT-PCR analysis indicated elevated levels of pro-angiogenic, anti-fibrotic, and anti-inflammatory factors such as SDF1, HGF, FGF2, and TGFb3. These findings suggested that HMGB1 fragment activated a self-tissue repair pathway, leading to improved cardiac function. The less-invasive intravenous administration of the HMGB1 fragment highlights its potential as a regenerative therapy for severe HF.

Discussion

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Cite This Study

Ito et al. (2026) studied Ischemic cardiomyopathy (porcine model) (n=12). Intravenous high mobility group box 1 (HMGB1) fragment vs. Normal saline was evaluated on Change in left ventricular ejection fraction (ΔLVEF) at 8 weeks (p=0.0015). Intravenous HMGB1 fragment significantly improved left ventricular ejection fraction by 11.0% compared to a 4.8% decrease in controls in a porcine ischemic cardiomyopathy model.

synapsesocial.com/papers/699010382ccff479cfe56d39 https://doi.org/10.1038/s41598-026-38592-7

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Intravenous high mobility group box 1 fragment improves cardiac function, fibrosis, and coronary flow in porcine ischemic cardiomyopathy model

Figures

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Intravenous high mobility group box 1 fragment improves cardiac function, fibrosis, and coronary flow in porcine ischemic cardiomyopathy model

Figures

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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