<i>A</i><i>ntrodia camphorata</i>attenuates cigarette smoke-induced ROS production, DNA damage, apoptosis, and inflammation in vascular smooth muscle cells, and atherosclerosis in ApoE-deficient mice

Yang, Hsin‐Ling; Korivi, Mallikarjuna; Chen, Cheng-Hsien; Peng, Wei-Jung; Chen, Chee‐Shan; Li, Meiling; Hsu, Li‐Sung; Liao, Jiunn‐Wang; Hseu, You‐Cheng

doi:10.1002/tox.22422

Cited by 16 publications

(7 citation statements)

References 53 publications

(175 reference statements)

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“…First, we clearly showed that CSE induced VSMC ferroptosis in vitro and caused medial VSMC loss in ex vivo aortas; however, the in vivo effect of CSE on the development of aortic aneurysm remains to be examined. Although no previous report has described animal models of AA and AD induced by CSE treatment, chronic CSE treatment for 2-5 mo has been shown to accelerate atherogenesis in atherosclerosis-prone mice and rabbits (37,39). Interestingly, the atherosclerotic lesions in CSE-treated rabbits were significantly decreased by treatment with vitamin E (37), a potent inhibitor of ferroptosis (10).…”

Section: H515mentioning

confidence: 99%

Cigarette smoke extract induces ferroptosis in vascular smooth muscle cells

Sampilvanjil

Karasawa

Yamada

et al. 2020

American Journal of Physiology-Heart and Circulatory Physiology

127

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Cigarette smoking is a major risk factor for aortic aneurysm and dissection; however, no causative link between smoking and these aortic disorders has been proven. In the present study, we investigated the mechanism by which cigarette smoke affects vascular wall cells and found that cigarette smoke extract (CSE) induced a novel form of regulated cell death termed ferroptosis in vascular smooth muscle cells (VSMCs). CSE markedly induced cell death in A7r5 cells and primary rat VSMCs, but not in endothelial cells, which was completely inhibited by specific ferroptosis inhibitors [ferrostatin-1 (Fer-1) and Liproxstatin-1] and an iron chelator (deferoxamine). CSE-induced VSMC death was partially inhibited by a GSH precursor ( N-acetyl cysteine) and an NADPH oxidase inhibitor [diphenyleneiodonium chloride (DPI)], but not by inhibitors of pan-caspases (Z-VAD), caspase-1 (Z-YVAD), or necroptosis (necrostatin-1). CSE also upregulated IL-1β, IL-6, TNF-α, matrix metalloproteinase (MMP)-2, MMP-9, and TIMP-1 (tissue inhibitor of metalloproteinase)in A7r5 cells, which was inhibited by Fer-1. Furthermore, CSE induced the upregulation of Ptgs2 mRNA, lipid peroxidation, and intracellular GSH depletion, which are key features of ferroptosis. VSMC ferroptosis was induced by acrolein and methyl vinyl ketone, major constituents of CSE. Furthermore, CSE caused medial VSMC loss in ex vivo aortas. Electron microscopy analysis showed mitochondrial damage and fragmentation in medial VSMCs of CSE-treated aortas. All of these manifestations were partially restored by Fer-1. These findings demonstrate that ferroptosis is responsible for CSE-induced VSMC death and suggest that ferroptosis is a potential therapeutic target for preventing aortic aneurysm and dissection. NEW & NOTEWORTHY Cigarette smoke extract (CSE)-induced cell death in rat vascular smooth muscle cells (VSMCs) was completely inhibited by specific ferroptosis inhibitors and an iron chelator. CSE also induced the upregulation of Ptgs2 mRNA, lipid peroxidation, and intracellular GSH depletion, which are key features of ferroptosis. CSE caused medial VSMC loss in ex vivo aortas. These findings demonstrate that ferroptosis is responsible for CSE-induced VSMC death.

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Section: H515mentioning

confidence: 99%

Cigarette smoke extract induces ferroptosis in vascular smooth muscle cells

Sampilvanjil

Karasawa

Yamada

et al. 2020

American Journal of Physiology-Heart and Circulatory Physiology

127

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“…It has been reported that oxidative stress and inflammation played vital roles in cerebral ischemia–reperfusion injury 29 . A previous research demonstrated that cigarette smoke exposure could activate several mechanisms including dyslipidemia, oxidative stress, and vascular inflammation, thereby leading to AS and participating the development of AS 30 . Moreover, PM2.5 also contributed to the progression of AS via causing endothelial dysfunction and inducing oxidative stress and systemic inflammation 31,32 .…”

Section: Discussionmentioning

confidence: 99%

“…29 A previous research demonstrated that cigarette smoke exposure could activate several mechanisms including dyslipidemia, oxidative stress, and vascular inflammation, thereby leading to AS and participating the development of AS. 30 Moreover, PM2.5 also contributed to the progression of AS via causing endothelial dysfunction and inducing oxidative stress and systemic inflammation. 31,32 Ox-LDL was verified to facilitate the formation of atherosclerotic plaque via inducing endothelial injury, foam cell formation from macrophages, endothelial apoptosis, and disruption of antioxidant capabilities.…”

Section: Asv Treatment Assuaged Ox-ldl-induced Injury In Huvecs By Ta...mentioning

confidence: 99%

Astragaloside IV protects against oxidized low‐density lipoprotein‐induced injury in human umbilical vein endothelial cells via the histone deacetylase 9 (HDAC9)/NF‐κB axis

Chen

et al. 2022

Environmental Toxicology

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Background: Atherosclerosis is a main cause of multiple cardiovascular diseases, and cell damage of human umbilical vein endothelial cells (HUVECs) was reported to participate in the development of atherosclerosis. In this study, we aimed to study the action of Astragaloside IV (ASV) on AS development using in vitro AS cell model.Methods: MTT assay, EdU staining assay, and flow cytometry were utilized for detection of cell proliferation and apoptosis, respectively. The protein expression of histone deacetylase 9 (HDAC9), Bax, Bcl-2, p-P65, P65, p-IκBα, and IκBα was gaged using western blot. The angiogenesis was evaluated by tube formation assay. The inflammatory response was evaluated by ELISA kits. SOD activity and MDA level were detected using the matched commercial kits. RT-qPCR was used for HDAC9 mRNA expression measurement.Results: Oxidized low-density lipoprotein (ox-LDL) significantly repressed cell proliferation, angiogenesis, and enhanced apoptosis, inflammation, and oxidative stress in HUVECs. ASV addition could alleviate ox-LDL-caused cell damage in HUVECs. Moreover, HDAC9 was overexpressed in AS patients and AS cell model. Functionally, HDAC9 knockdown also exhibited the protective role in ox-LDL-treated HUVECs. In addition, ASV treatment protected against ox-LDL-induced damage in HUVECs via targeting HDAC9. ASV could inactivate the NF-κB pathway via regulating HDAC9 in AS cell model. Conclusion:ASV exerted the protective effects on ox-LDL-induced damage in HUVECs through the HDAC9/NF-κB axis.

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“…In Taiwan, certain herbal extracts, such as Antrodia camphorata , have shown considerable therapeutic potential for atherosclerosis because of anti-inflammatory activity in cellular and preclinical studies [ 24 ] (Yang et al, 2017). A previous study disclosed that antcin K, an active triterpenoid extracted from fruiting bodies of Antrodia camphorate inhibited the production of pro-inflammatory cytokines and vascular cell adhesion molecule 1 (VCAM-1) in rheumatoid synovial fibroblasts [ 25 , 26 ] (Achudhan et al, 2021; 2022).…”

Section: Introductionmentioning

confidence: 99%

Botanical Antcin K Alleviates High-Fat Damage in Palm Acid Oil-Treated Vascular Endothelial Cells and Macrophages

Nguyen

Shen

et al. 2022

Plants

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Lipid metabolism disorder is the most critical risk factor for atherosclerosis, and the process involves lipid deposition in the arterial intima. In Taiwan, antcin K, an active triterpenoid from the fruiting bodies of Antrodia camphorata, has been considered a potential lipid-lowering agent. Despite this, the possible therapeutic mechanisms of antcin K remain unclear. To explore the crucial role of botanical antcin K in reducing atherosclerotic plaque, we used SVEC4-10 vascular endothelial cells and RAW264.7 macrophages with palm acid oil-induced high-fat damage as our cell models. Our results showed through using the DPPH assay that antcin K had excellent free radical scavenging ability. Antcin K treatment can significantly alleviate the high-fat damage and reduce the levels of inflammatory factors of TNF-α and IL-1β in vascular endothelial cells and macrophages, as shown through MTT assay and ELISA. Furthermore, antcin K treatment can effectively enhance migration ability and clear lipid deposition in macrophages, as shown by using cell migration assay and oil red O staining. When stained with immunofluorescence, antcin K was shown to significantly decrease the expression of adhesion molecules of vascular cell adhesion molecule 1 (VCAM-1) in vascular endothelial cells involved in monocyte migration and inflammation. Antcin K not only reduced the expression of the CD36 scavenger receptor but also augmented the expression of Kruppel-like factor 4 (KLF4) transcription factor in macrophages, which inhibits the transformation of macrophages into foam cells underlying the pathological process of atherosclerosis. Taking our findings into account, we suggested that botanical antcin K could have therapeutic potential for the treatment of atherosclerosis.

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Antrodia camphorataattenuates cigarette smoke-induced ROS production, DNA damage, apoptosis, and inflammation in vascular smooth muscle cells, and atherosclerosis in ApoE-deficient mice

Cited by 16 publications

References 53 publications

Cigarette smoke extract induces ferroptosis in vascular smooth muscle cells

Cigarette smoke extract induces ferroptosis in vascular smooth muscle cells

Astragaloside IV protects against oxidized low‐density lipoprotein‐induced injury in human umbilical vein endothelial cells via the histone deacetylase 9 (HDAC9)/NF‐κB axis

Botanical Antcin K Alleviates High-Fat Damage in Palm Acid Oil-Treated Vascular Endothelial Cells and Macrophages

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