Research Paper Volume 12, Issue 1 pp 193—203
Interleukin-12p35 deficiency enhances mitochondrial dysfunction and aggravates cardiac remodeling in aging mice
- 1 Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan 430060, China
- 2 Department of Thyroid Breast Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China
- 3 Emergency and Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, and Beijing Lab for Cardiovascular Precision Medicine, Beijing 100029, China
- 4 Department of Cardiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China
Received: May 7, 2019 Accepted: December 5, 2019 Published: January 4, 2020
https://doi.org/10.18632/aging.102609How to Cite
Abstract
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.