Abstract：
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major 21st-century epidemic. T2DM elevates the risk of myocardial infarction and heart failure while also reducinges survival rates. Recently Ferroptosis has been found to be involved in the development of various cardiovascular diseases. TRPV1 is also a potential therapeutic target for cardioprotection. This study explores whether capsaicin, a transient receptor potential vanilloid receptor 1 (TRPV1) agonist, can prevent diabetic myocardial infarction-induced injury by inhibiting ferroptosis.
METHODS: T2DM model was induced by high-fat diet (HFD) feeding combined with streptozocin (STZ) injections, and the diabetic mice were treated with capsaicin(0.015 %) in their food. Myocardial infarction model was established as well. Mouse\' general characteristics, cardiac function, and morphological histology were observed and analyzed. RNA-seq was used to investigate the possible mechanism of injury in AC16 cardiomyocytes cultured with high glucose and hypoxia. In addition, the potential mechanism of capsaicin against injury was further investigated in AC16 cardiomyocytes cultured with high glucose and hypoxia.
RESULTS: The RNA-seq analysis revealed that ferroptosis was associated with cell death induced by high-glucose in combination with hypoxia, and CAP treatment could effectively inhibit ferroptosis to enhance cell survival. In vivo studies demonstrated that CAP treatment significantly improved post-MI cardiac function, attenuated myocardial inflammation and fibrosis. Furthermore, it was observed that CAP reduced ferroptosis levels by activating TRPV1 in the heart, upregulating Nrf2 expression, promoting Nrf2 nuclear translocation and increasing the expression of the Nrf2 downstream molecule Heme oxygenase-1 (HMOX1).
CONCLUSIONS: Dietary capsaicin may inhibit cardiomyocyte ferroptosis through activation of myocardial TRPV1 and Nrf2/HMOX1 signaling pathway, which in turn exerts a protective effect on the myocardium after myocardial infarction in type 2 diabetic mice.
METHODS: T2DM model was induced by high-fat diet (HFD) feeding combined with streptozocin (STZ) injections, and the diabetic mice were treated with capsaicin(0.015 %) in their food. Myocardial infarction model was established as well. Mouse\' general characteristics, cardiac function, and morphological histology were observed and analyzed. RNA-seq was used to investigate the possible mechanism of injury in AC16 cardiomyocytes cultured with high glucose and hypoxia. In addition, the potential mechanism of capsaicin against injury was further investigated in AC16 cardiomyocytes cultured with high glucose and hypoxia.
RESULTS: The RNA-seq analysis revealed that ferroptosis was associated with cell death induced by high-glucose in combination with hypoxia, and CAP treatment could effectively inhibit ferroptosis to enhance cell survival. In vivo studies demonstrated that CAP treatment significantly improved post-MI cardiac function, attenuated myocardial inflammation and fibrosis. Furthermore, it was observed that CAP reduced ferroptosis levels by activating TRPV1 in the heart, upregulating Nrf2 expression, promoting Nrf2 nuclear translocation and increasing the expression of the Nrf2 downstream molecule Heme oxygenase-1 (HMOX1).
CONCLUSIONS: Dietary capsaicin may inhibit cardiomyocyte ferroptosis through activation of myocardial TRPV1 and Nrf2/HMOX1 signaling pathway, which in turn exerts a protective effect on the myocardium after myocardial infarction in type 2 diabetic mice.
摘要：
背景：2型糖尿病（T2DM）是21世纪的主要流行病。T2DM会增加心肌梗死和心力衰竭的风险，同时也会降低生存率。最近发现Ferroptosis参与了各种心血管疾病的发展。TRPV1也是心脏保护的潜在治疗靶标。这项研究探讨了辣椒素，瞬时受体电位香草素受体1（TRPV1）激动剂，可以通过抑制铁蛋白凋亡来预防糖尿病心肌梗死引起的损伤。
方法：采用高脂饮食（HFD）喂养联合链脲佐菌素（STZ）注射诱导T2DM模型，糖尿病小鼠用食物中的辣椒素(0.015%)治疗。建立心肌梗死模型。鼠标的一般特征，心功能,进行形态学观察和组织学分析。RNA-seq用于研究高糖和低氧培养的AC16心肌细胞损伤的可能机制。此外,进一步研究了辣椒素在高糖缺氧条件下培养的AC16心肌细胞抗损伤的潜在机制。
结果：RNA-seq分析显示，铁凋亡与高糖联合缺氧诱导的细胞死亡有关，CAP处理能有效抑制铁凋亡,增强细胞存活。体内研究表明，CAP治疗显著改善MI后心功能，减轻心肌炎症和纤维化。此外，据观察，CAP通过激活心脏中的TRPV1来降低铁凋亡水平，上调Nrf2表达，促进Nrf2核转位并增加Nrf2下游分子血红素加氧酶-1（HMOX1）的表达。
结论：饮食辣椒素可能通过激活心肌TRPV1和Nrf2/HMOX1信号通路抑制心肌细胞铁性凋亡，进而对2型糖尿病小鼠心肌梗死后的心肌产生保护作用。
方法：采用高脂饮食（HFD）喂养联合链脲佐菌素（STZ）注射诱导T2DM模型，糖尿病小鼠用食物中的辣椒素(0.015%)治疗。建立心肌梗死模型。鼠标的一般特征，心功能,进行形态学观察和组织学分析。RNA-seq用于研究高糖和低氧培养的AC16心肌细胞损伤的可能机制。此外,进一步研究了辣椒素在高糖缺氧条件下培养的AC16心肌细胞抗损伤的潜在机制。
结果：RNA-seq分析显示，铁凋亡与高糖联合缺氧诱导的细胞死亡有关，CAP处理能有效抑制铁凋亡,增强细胞存活。体内研究表明，CAP治疗显著改善MI后心功能，减轻心肌炎症和纤维化。此外，据观察，CAP通过激活心脏中的TRPV1来降低铁凋亡水平，上调Nrf2表达，促进Nrf2核转位并增加Nrf2下游分子血红素加氧酶-1（HMOX1）的表达。
结论：饮食辣椒素可能通过激活心肌TRPV1和Nrf2/HMOX1信号通路抑制心肌细胞铁性凋亡，进而对2型糖尿病小鼠心肌梗死后的心肌产生保护作用。
