Reference - Detail
| RRC ID | 58497 |
|---|---|
| Author | Sampilvanjil A, Karasawa T, Yamada N, Komada T, Higashi T, Baatarjav C, Watanabe S, Kamata R, Ohno N, Takahashi M. |
| Title | Cigarette smoke extract induces ferroptosis in vascular smooth muscle cells. |
| Journal | Am J Physiol Heart Circ Physiol |
| Abstract |
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. |
| Volume | 318(3) |
| Pages | H508-H518 |
| Published | 2020-3-1 |
| DOI | 10.1152/ajpheart.00559.2019 |
| PMID | 31975626 |
| MeSH | Animals Cell Death / drug effects Cell Line Cyclohexylamines / pharmacology Deferoxamine / pharmacology Endothelial Cells / drug effects Endothelial Cells / metabolism Ferroptosis / drug effects* Male Matrix Metalloproteinase 2 / metabolism Matrix Metalloproteinase 9 / metabolism Muscle, Smooth, Vascular / metabolism* Myocytes, Smooth Muscle / drug effects Myocytes, Smooth Muscle / metabolism* NADPH Oxidases / metabolism Phenylenediamines / pharmacology Quinoxalines / pharmacology Rats Rats, Sprague-Dawley Siderophores / pharmacology Smoke* Spiro Compounds / pharmacology Tissue Inhibitor of Metalloproteinase-1 / metabolism |
| IF | 3.864 |
| Times Cited | 1 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 17 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| DNA material | CS-CA-MCS (RDB05963) |
| Human and Animal Cells | 10T1/2(RCB0247) |