Interleukin-12p35 deficiency enhances mitochondrial dysfunction and aggravates cardiac remodeling in aging mice.

Our previous studies have demonstrated that interleukin-12p35 knockout (IL-12p35 KO) regulates the progression of various cardiovascular diseases, such as acute cardiac injury and hypertension. The aims of this study were to investigate whether IL-12p35 KO affects aging-related cardiac remodeling and to explore the possible mechanisms. First, the effects of IL-12p35 KO on heart structure and function were detected, and the results showed that IL-12p35 KO exacerbated cardiac remodeling and increased cardiac senescence-related protein levels in aged mice. In addition, whether IL-12p35 KO regulates cardiac senescence-related protein expression, cardiac mitochondrial dysfunction and cardiomyocyte apoptosis was also investigated. IL-12p35 KO increased mitochondrial calcium fluorescence intensity and ROS fluorescence intensity, while it reduced mitochondrial membrane potential. Furthermore, reduced mitochondrial complex (I-IV) activity and ATP levels and increased apoptosis-inducing factor (AIF)-related cardiomyocyte apoptosis were observed in aged IL-12p35 KO mice compared with wild-type mice. Our results demonstrate that aging is aggravated by IL-12p35 KO and that the mechanism may be related to exacerbation of mitochondrial dysfunction and AIF-related cardiomyocyte apoptosis.

Citation

Jing Ye, Yuan Wang, Zhen Wang, Ling Liu, Zicong Yang, Di Ye, Menglong Wang, Yao Xu, Jishou Zhang, Mengmeng Zhao, Jianfang Liu, Yingzhong Lin, Qingwei Ji, Jun Wan. Interleukin-12p35 deficiency enhances mitochondrial dysfunction and aggravates cardiac remodeling in aging mice. Aging. 2020 Jan 04;12(1):193-203

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PMID: 31901899

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