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Cyclophilin D deficiency protects against the development of mitochondrial ROS and cellular inflammation in aorta
Xiaojing Liu1, Heng Du2, Dan Chen3
1Deparment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, China; Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Jinan, Shandong, 250021, China; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong, 250021, China.
Introduction:
Inflammation and oxidative stress are closely correlated in the pathology of cardiovascular disease. Mitochondrial cyclophilin D (CypD), the important modulator for mPTP opening, is increasingly recognized as a key regulator of cellular ROS generation. Besides, its association with cell inflammation is also being discovered. However, the effects of CypD in modulating vascular inflammatory response is unknown. We sought to investigate whether CypD deficiency attenutes vascular inflammation under physical conditions.
Methods And Results:
We adopted CypD KO mouse and their littermate controls to observe the effects of CypD deficiency on aortic mitochondrial functions and vascular inflammation. As we found in our study, we confirmed that under physical conditions, CypD deficiency enhanced mouse whole body metabolic status, increased aortic mitochondrial complex III activity and decreased mitochondrial ROS generation. Functionally, CypD deficiency also attenuated inflammatory molecules expression, including VCAM-1, IL-6 and TNF-α in mouse aorta.
Conclusions:
Our results review that mitochondrial CypD is involved in the regulation of inflammation in aorta and provide insights that blocking mitochondrial CypD enhances vascular resistance to inflammatory injuries.
Insights
Mitochondrial cyclophilin D (CypD) deficiency improves metabolic health and reduces vascular inflammation. Blocking CypD enhances resistance to inflammatory injuries in the aorta, offering a potential therapeutic target for cardiovascular disease.
Area of Science:
- Cardiovascular Disease Research
- Mitochondrial Biology
- Inflammation and Immunology
Background:
- Inflammation and oxidative stress are key drivers of cardiovascular disease pathology.
- Mitochondrial cyclophilin D (CypD) regulates mitochondrial reactive oxygen species (ROS) generation and is linked to cellular inflammation.
- The role of CypD in vascular inflammatory responses remains largely unexplored.
Purpose of the Study:
- To investigate the impact of CypD deficiency on vascular inflammation under physical conditions.
- To determine if CypD plays a role in modulating the inflammatory response within the aorta.
Main Methods:
- Utilized CypD knockout (KO) mice and littermate controls.
- Assessed aortic mitochondrial function, including complex III activity and ROS generation.
- Quantified the expression of inflammatory markers (VCAM-1, IL-6, TNF-α) in mouse aortas.
Main Results:
- CypD deficiency improved whole-body metabolic status in mice.
- Aortic mitochondria showed increased complex III activity and reduced ROS generation in CypD KO mice.
- Expression of key inflammatory molecules (VCAM-1, IL-6, TNF-α) was attenuated in the aorta of CypD-deficient mice.
Conclusions:
- Mitochondrial CypD is implicated in regulating aortic inflammation.
- Blocking CypD enhances vascular resilience against inflammatory damage.
- Targeting mitochondrial CypD presents a potential strategy for mitigating vascular inflammatory injuries.
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