著者

Lei Zhang Baoli Zhang Ying Yu Jingfeng Wang Jian Wu Yangang Su Hong Jiang Yunzeng Zou Junbo Ge

出版者

International Heart Journal Association

雑誌

International Heart Journal (ISSN:13492365)

巻号頁・発行日

vol.62, no.1, pp.162-170, 2021-01-30 (Released:2021-01-30)

参考文献数

44

被引用文献数

5

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High-mobility group box 1 (HMGB1) is increased in the myocardium under pressure overload (PO) and is involved in PO-induced cardiac remodeling. The mechanisms of the upregulation of cardiac HMGB1 expression have not been fully elucidated. In the present study, a mouse transverse aortic constriction (TAC) model was used, and an angiotensin II (Ang II) type 1 (AT1) receptor inhibitor (losartan) or Ang II type 2 (AT2) receptor inhibitor (PD123319) was administrated to mice for 14 days. Cardiac myocytes were cultured and treated with Ang II for 5 minutes to 48 hours conditionally with the blockage of the AT1 or AT2 receptor. TAC-induced cardiac hypertrophy was observed at 14 days after the operation, which was partially reversed by losartan, but not by PD123319. Similarly, the upregulated HMGB1 expression levels observed in both the serum and myocardium induced by TAC were reduced by losartan. Elevated cardiac HMGB1 protein levels, but not mRNA or serum levels, were significantly decreased by PD123319. Furthermore, HMGB1 expression levels in culture media and cardiac myocytes were increased following Ang II treatment in vitro, positively associated with the duration of treatment. Similarly, Ang II-induced upregulation of HMGB1 in vitro was inhibited by both losartan and PD123319. These results suggest that upregulation of HMGB1 in serum and myocardium under PO, which are partially derived from cardiac myocytes, may be induced by Ang II via the AT1 and AT2 receptors. Additionally, amelioration of PO-induced cardiac hypertrophy following losartan treatment may be associated with the reduction of HMGB1 expression through the AT1 receptor.