Iron deficiency exacerbates aortic medial degeneration by inducing excessive mitochondrial fission

Zhong, Xiaohan; Wu, Qi; Wang, Zhiwei; Zhang, Min; Zheng, Shu-Jian; Shi, Feng; Chen, Yuanyang; Che, Yanjia; Yuan, Shenfang; Xing, Kai

doi:10.1039/d2fo01084d

Cited by 6 publications

(1 citation statement)

References 47 publications

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“…Dynamin-related protein 1 (Drp1) and mitochondrial fission factor (Mff) are both localized on MERCs to function ( Cherubini et al, 2020 ; Luan et al, 2021 ; Zhong et al, 2022 ). Drp1 is the important effector molecule in mitochondrial fission.…”

Section: Biological Functions Of Mercsmentioning

confidence: 99%

Mitochondria-endoplasmic reticulum contacts in sepsis-induced myocardial dysfunction

Jiang

Wang

et al. 2022

Front. Cell Dev. Biol.

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Mitochondrial and endoplasmic reticulum (ER) are important intracellular organelles. The sites that mitochondrial and ER are closely related in structure and function are called Mitochondria-ER contacts (MERCs). MERCs are involved in a variety of biological processes, including calcium signaling, lipid synthesis and transport, autophagy, mitochondrial dynamics, ER stress, and inflammation. Sepsis-induced myocardial dysfunction (SIMD) is a vital organ damage caused by sepsis, which is closely associated with mitochondrial and ER dysfunction. Growing evidence strongly supports the role of MERCs in the pathogenesis of SIMD. In this review, we summarize the biological functions of MERCs and the roles of MERCs proteins in SIMD.

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Section: Biological Functions Of Mercsmentioning

confidence: 99%

Mitochondria-endoplasmic reticulum contacts in sepsis-induced myocardial dysfunction

Jiang

Wang

et al. 2022

Front. Cell Dev. Biol.

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Ciprofloxacin Accelerates Angiotensin-II-Induced Vascular Smooth Muscle Cells Senescence Through Modulating AMPK/ROS pathway in Aortic Aneurysm and Dissection

Zeng,

Liang,

Huang

et al. 2024

Cardiovasc Toxicol

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Aortic aneurysm and dissection (AAD) is a cardiovascular disease that poses a severe threat to life and has high morbidity and mortality rates. Clinical and animal-based studies have irrefutably shown that fluoroquinolones, a commonly prescribed antibiotic for treating infections, significantly increase the risk of AAD. Despite this, the precise mechanism by which fluoroquinolones cause AAD remains unclear. Therefore, this study aims to investigate the molecular mechanism and role of Ciprofloxacin definitively—a type of fluoroquinolone antibiotic—in the progression of AAD. Aortic transcriptome data were collected from GEO datasets to detect the genes and pathways expressed differently between healthy donors and AAD patients. Human primary Vascular Smooth Muscle Cells (VSMCs) were isolated from the aorta. After 72 h of exposure to 110ug/ml Ciprofloxacin or 100 nmol/L AngII, either or combined, the senescent cells were identified through SA-β-gal staining. MitoTracker staining was used to examine the morphology of mitochondria in each group. Cellular Reactive Oxygen Species (ROS) levels were measured using MitoSox and DCFH-DA staining. Western blot assay was performed to detect the protein expression level. We conducted an analysis of transcriptome data from both healthy donors and patients with AAD and found that there were significant changes in cellular senescence-related signaling pathways in the latter group. We then isolated and identified human primary VSMCs from healthy donors (control-VSMCs) and patients' (AAD-VSMCs) aortic tissue, respectively. We found that VSMCs from patients exhibited senescent phenotype as compared to control-VSMCs. The higher levels of p21 and p16 and elevated SA-β-gal activity demonstrated this. We also found that pretreatment with Ciprofloxacin promoted angiotensin-II-induced cellular senescence in control-VSMCs. This was evidenced by increased SA-β-gal activity, decreased cell proliferation, and elevation of p21 and p16 protein levels. Additionally, we found that Angiotensin-II (AngII) induced VSMC senescence by promoting ROS generation. We used DCFH-DA and mitoSOX staining to identify that Ciprofloxacin and AngII pretreatment further elevated ROS levels than the vehicle or alone group. Furthermore, JC-1 staining showed that mitochondrial membrane potential significantly declined in the Ciprofloxacin and AngII combination group compared to others. Compared to the other three groups, pretreatment of Ciprofloxacin plus AngII could further induce mitochondrial fission, demonstrated by mitoTracker staining and western blotting assay. Mechanistically, we found that Ciprofloxacin impaired the balance of mitochondrial fission and fusion dynamics in VSMCs by suppressing the phosphorylation of AMPK signaling. This caused mitochondrial dysfunction and ROS generation, thereby elevating AngII-induced cellular senescence. However, treatment with the AMPK activator partially alleviated those effects. Our data indicate that Ciprofloxacin may accelerate AngII-induced VSMC senescence through...

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Stearic acid alleviates aortic medial degeneration through maintaining mitochondrial dynamics homeostasis via inhibiting JNK/MAPK signaling

Wang,

Xie,

et al. 2024

iScience

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Iron deficiency exacerbates aortic medial degeneration by inducing excessive mitochondrial fission

Abstract: Iron deficiency (ID) is a global nutritional deficiency that was shown to be involved in the pathogenesis of aortic aneurysm and dissection (AAD) in our previous studies. Some studies suggested...

Cited by 6 publications

References 47 publications

Mitochondria-endoplasmic reticulum contacts in sepsis-induced myocardial dysfunction

Mitochondria-endoplasmic reticulum contacts in sepsis-induced myocardial dysfunction

Ciprofloxacin Accelerates Angiotensin-II-Induced Vascular Smooth Muscle Cells Senescence Through Modulating AMPK/ROS pathway in Aortic Aneurysm and Dissection

Stearic acid alleviates aortic medial degeneration through maintaining mitochondrial dynamics homeostasis via inhibiting JNK/MAPK signaling

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