Zhang Junxia, Zhao Chengcheng, Zhang Wenjia, Zhang Mao, Li Fan, Shang Haibao, Zheng Wen, Li Yingjia, Quan Li, Li Xiaochuan, Li Huihui, Wang Luyun, Wen Zheng, Zhou Yiwu, Wang Dao Wen, Dong Erdan, Chen Chen, Zhang Yan
Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing, 100191, China.
Institute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Sci China Life Sci. 2025 Aug 28. doi: 10.1007/s11427-025-2939-1.
Viral myocarditis, an inflammatory heart disorder caused by viral infections, often leads to poor outcomes due to the lack of effective prevention and treatment strategies. Despite the characteristic feature of cardiomyocyte death in this condition, the underlying mechanisms and potential therapeutic approaches remain poorly understood. Traditional Chinese medicine (TCM), despite its extensive history in treating various diseases, has not yet been approved for the treatment of viral myocarditis. Here, we screened six TCM patent injections recommended by clinical practice guidelines for treating cardiovascular diseases and discovered that Danhong Injection (DHI) markedly reduced cardiomyocyte death induced by Coxsackievirus B3 (CVB3). Additionally, in a CVB3-infected mouse model of viral myocarditis, DHI treatment notably alleviated cardiomyocyte death (including apoptosis, necroptosis and pyroptosis), as well as inflammation, cardiac dysfunction, and mortality. Mechanistically, DHI exerted its protective effects by inhibiting CaMKII through its active monomer Dihydrotanshinone I (Dih-I), identified as a CaMKII inhibitor. In viral myocarditis patients, CaMKII phosphorylation was upregulated in the hearts. The anti-inflammatory properties and CaMKII inhibition effects of DHI were further validated in primary human peripheral blood mononuclear cells. Our findings not only demonstrate the central role of CaMKII-mediated cardiomyocyte death in the progression of viral myocarditis, but also highlight DHI as a promising therapeutic intervention for managing viral myocarditis-induced cardiac injury and related pathological response.
病毒性心肌炎是一种由病毒感染引起的炎症性心脏病,由于缺乏有效的预防和治疗策略,往往导致不良后果。尽管在这种情况下心肌细胞死亡是其特征性表现,但潜在机制和潜在治疗方法仍知之甚少。传统中医(TCM)虽然在治疗各种疾病方面有着悠久的历史,但尚未被批准用于治疗病毒性心肌炎。在此,我们筛选了临床实践指南推荐的六种用于治疗心血管疾病的中药专利注射剂,发现丹红注射液(DHI)显著减少了柯萨奇病毒B3(CVB3)诱导的心肌细胞死亡。此外,在CVB3感染的病毒性心肌炎小鼠模型中,DHI治疗显著减轻了心肌细胞死亡(包括凋亡、坏死性凋亡和焦亡)以及炎症、心脏功能障碍和死亡率。机制上,DHI通过其活性单体二氢丹参酮I(Dih-I)抑制CaMKII发挥其保护作用,Dih-I被鉴定为一种CaMKII抑制剂。在病毒性心肌炎患者中,心脏中CaMKII磷酸化上调。DHI的抗炎特性和CaMKII抑制作用在原代人外周血单核细胞中得到进一步验证。我们的研究结果不仅证明了CaMKII介导的心肌细胞死亡在病毒性心肌炎进展中的核心作用,还突出了DHI作为一种有前景的治疗干预手段,可用于管理病毒性心肌炎诱导的心脏损伤和相关病理反应。
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