AT1 receptor blocker inhibits HMGB1 expression in pressure overload-induced acute cardiac dysfunction by suppressing the MAPK/NF-κB signaling pathway

• Published in: Clinical and experimental hypertension (1993) 2022-01, Vol.44 (1), p.93-99
• Main Authors: Zhang, Lei, Zhang, Baoli, Wu, Jian, Zou, Yunzeng, Jiang, Hong, Ge, Junbo
• Format: Article
• Language: English
• Subjects: acute cardiac dysfunction; Angiotensin II type 1 receptor blocker; Angiotensin II Type 1 Receptor Blockers - pharmacology; Animals; cardiac remodeling; Heart Diseases; high-mobility group box 1; HMGB1 Protein - metabolism; Mice; Mitogen-Activated Protein Kinases - metabolism; NF-kappa B - metabolism; pressure overload; Receptor, Angiotensin, Type 1; Signal Transduction
• ISSN: 1064-1963; 1525-6006
• DOI: 10.1080/10641963.2021.1996588

High-mobility group box 1 (HMGB1) expression not only peaks during the early phase of pressure overload (PO), but also serves a role in the pathogenesis of PO-induced cardiac remodeling. Meanwhile, angiotensin II type 1 (AT1) receptor blockers reverse PO-induced cardiac remodeling and repress the secretion of inflammatory factors. However, whether AT1 receptor inhibitors decrease HMGB1 expression in the early stages of PO remains unknown. PO mouse models were established using transverse aortic constriction (TAC), in which losartan was administrated. Transthoracic echocardiography was performed 3 days after the operation, and serum and cardiac HMGB1 expression, as well as the expression levels of related proteins were measured. PO-induced acute cardiac dysfunction was observed 3 days after TAC, and was subsequently slightly, but not significantly relieved by losartan. The expression levels of HMGB1, tumor necrosis factor-α and interleukin-6 in both the serum and myocardium were upregulated in response to TAC, while they were significantly reduced by losartan. Moreover, the phosphorylation of extracellular signal-regulated kinases, p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in the myocardium were significantly increased under PO, and this was also prevented by losartan. These data suggest that losartan may downregulate the expression of HMGB1 in acute cardiac dysfunction induced by PO by inhibiting the MAPKs/NF-κB signaling pathway, which indicates a novel beneficial role of AT1 receptor antagonists in ameliorating cardiac remodeling under PO.