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.
Does intravenous HMGB1 fragment improve cardiac function, coronary flow, and cardiac fibrosis in a porcine ischemic cardiomyopathy model?
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.
Absolute Event Rate: 11% vs -4.8%
p-value: p=0.0015
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.
Ito et al. (Wed,) conducted a other in 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.