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年龄相关的心脏和代谢表型变化与小鼠炎症细胞因子和抗氧化状态有关。

Age-Related Shift in Cardiac and Metabolic Phenotyping Linked to Inflammatory Cytokines and Antioxidant Status in Mice.

机构信息

National Institute of Health and Medical Research (INSERM) U1297, CEDEX 4, 31432 Toulouse, France.

University of Toulouse III, CEDEX 9, 31062 Toulouse, France.

出版信息

Int J Mol Sci. 2023 Oct 31;24(21):15841. doi: 10.3390/ijms242115841.

Abstract

Age-related alterations in cardiac function, metabolic, inflammatory and antioxidant profiles are associated with an increased risk of cardiovascular mortality and morbidity. Here, we examined cardiac and metabolic phenotypes in relation to inflammatory status and antioxidant capacity in young, middle-aged and old mice. Real-time reverse transcription-polymerase chain reactions were performed on myocardium and immunoassays on plasma. Left ventricular (LV) structure and function were assessed by echocardiography using high-frequency ultrasound. Middle-aged mice exhibited an altered metabolic profile and antioxidant capacity compared to young mice, whereas myocardial expression of inflammatory factors (TNFα, IL1β, IL6 and IL10) remained unchanged. In contrast, old mice exhibited increased expression of inflammatory cytokines and plasma levels of resistin compared to young and middle-aged mice ( < 0.05). The pro-inflammatory signature of aged hearts was associated with alterations in glutathione redox homeostasis and elevated contents of 4-hydroxynonenal (4-HNE), a marker of lipid peroxidation and oxidative stress. Furthermore, echocardiographic parameters of LV systolic and diastolic functions were significantly altered in old mice compared to young mice. Taken together, these findings suggest age-related shifts in cardiac phenotype encompass the spectrum of metabo-inflammatory abnormalities and altered redox homeostasis.

摘要

年龄相关的心脏功能、代谢、炎症和抗氧化状态的改变与心血管死亡率和发病率的增加有关。在这里,我们研究了与炎症状态和抗氧化能力相关的年轻、中年和老年小鼠的心脏和代谢表型。实时逆转录聚合酶链反应在心肌中进行,免疫测定在血浆中进行。使用高频超声通过超声心动图评估左心室(LV)结构和功能。与年轻小鼠相比,中年小鼠表现出代谢特征和抗氧化能力的改变,而心肌中炎症因子(TNFα、IL1β、IL6 和 IL10)的表达保持不变。相比之下,与年轻和中年小鼠相比,老年小鼠表现出炎症细胞因子的表达增加和血浆抵抗素水平升高(<0.05)。老年心脏的促炎特征与谷胱甘肽氧化还原平衡的改变以及脂质过氧化和氧化应激的标志物 4-羟壬烯醛(4-HNE)含量的升高有关。此外,与年轻小鼠相比,老年小鼠的左心室收缩和舒张功能的超声心动图参数明显改变。综上所述,这些发现表明,与年龄相关的心脏表型变化包括代谢炎症异常和氧化还原平衡改变的范围。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bf8/10650425/161ba0c21c63/ijms-24-15841-g001.jpg

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