Key result
Loss of endogenous HMGB2 in mice exacerbated cardiac dysfunction and accelerated heart failure development following pressure overload induced by transverse aorta constriction.
Why the study?
Although HMGB2 loss causes cardiomyocyte hypertrophy in vitro, its in vivo function in the heart had not been assessed.
Loss of endogenous HMGB2 exacerbates cardiac dysfunction and heart failure progression in a mouse model of pressure overload, suggesting a cardioprotective role for HMGB2.
Hypothesis-generating for HMGB2-targeted therapy in heart failure; leaves open relevance to human pressure-overload states.
BACKGROUND: The rapid increase in the number of heart failure (HF) patients in parallel with the increase in the number of older people is receiving attention worldwide. HF not only increases mortality but decreases quality of life, creating medical and social problems. Thus, it is necessary to define molecular mechanisms underlying HF development and progression. HMGB2 is a member of the high-mobility group superfamily characterized as nuclear proteins that bind DNA to stabilize nucleosomes and promote transcription. A recent in vitro study revealed that HMGB2 loss in cardiomyocytes causes hypertrophy and increases HF-associated gene expression. However, it's in vivo function in the heart has not been assessed. METHODS AND RESULTS: mice had worsened cardiac dysfunction after TAC surgery, predisposing mice to HF development and progression. CONCLUSIONS: This study demonstrates that upregulation of cardiac HMGB2 is an adaptive response to cardiac stress, and that loss of this response could accelerate cardiac dysfunction, suggesting that HMGB2 plays a cardioprotective role.
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Sato et al. (2018) studied Heart failure. Hmgb2 knockout vs. Wild-type mice was evaluated on Cardiac dysfunction and fractional shortening after transverse aorta constriction. Loss of endogenous HMGB2 in mice exacerbated cardiac dysfunction and accelerated heart failure development following pressure overload induced by transverse aorta constriction.
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