Cardiac growth and remodelling are key biological processes influencing the physiological performance of the heart, and a previous study showed a critical role for intracellular HMGB1 in vitro. However, the in vivo study, which used conditional Hmgb1 ablation, did not show a significant effect on cellular or organic function. We have demonstrated the extracellular effect of HMGB1 as a pro-inflammatory molecule on cardiac remodelling. In this study, we found that HMGB1 deletion by cTnT-Cre in mouse hearts altered glucocorticoid receptor (GR) function and glycolipid metabolism, eventually leading to growth retardation, small heart and heart failure. The subcellular morphology did not show a significant change caused by HMGB1 knockout. The heart showed significant elevation of glycolysis, free fatty acid deposition and related enzyme changes. Transcriptomic analysis revealed a list of differentially expressed genes that coincide with glucocorticoid receptor function in neonatal mice and a significant increase in inflammatory genes in adult mice. Cardiac HMGB1 knockout led to a series of changes in PGC-1α, UCP3 and GyK, which were the cause of metabolic changes and further impacted cardiac function. Ckmm-Cre Hmgb1^fl/fl mice did not show a specific phenotype, which was consistent with the reported negative result of cardiomyocyte-specific Hmgb1 deletion via MHC-Cre. We concluded that HMGB1 plays essential roles in maintaining normal cardiac growth, and different phenotype from cardiac-specific HMGB1-deficient mice may be caused by the cross with mice of different Cre strains.

心脏的生长和重塑是影响心脏生理性能的关键生物学过程，一项先前的研究显示了体外细胞内HMGB1的关键作用。但是，使用条件性Hmgb1消融的体内研究并未显示出对细胞或有机功能的显着影响。我们已经证明HMGB1作为促炎症分子对心脏重塑的细胞外作用。在这项研究中，我们发现cTnT-Cre在小鼠心脏中删除HMGB1会改变糖皮质激素受体（GR）的功能和糖脂代谢，最终导致生长迟缓，小心脏和心力衰竭。亚细胞形态没有显示出由HMGB1基因敲除引起的显着变化。心脏显示糖酵解，游离脂肪酸沉积和相关酶的变化明显升高。转录组学分析揭示了一系列差异表达的基因，这些基因与新生小鼠的糖皮质激素受体功能一致，成年小鼠的炎症基因显着增加。心脏HMGB1敲除导致PGC-1α，UCP3和GyK发生一系列变化，这是代谢变化的原因，并进一步影响心脏功能。Ckmm-Cre Hmgb1^{fl / fl}小鼠未显示特异性表型，这与报道的通过MHC-Cre心肌细胞特异性Hmgb1缺失的阴性结果相一致。我们得出的结论是，HMGB1在维持正常的心脏生长中起着重要作用，与心脏特异性HMGB1缺陷型小鼠的不同表型可能是由与不同Cre品系的小鼠杂交引起的。