Effect of Cigarette Smoke Extract on Neonatal Porcine Vascular Smooth Muscle Cells

2001 ◽  
Vol 170 (2) ◽  
pp. 130-136 ◽  
Author(s):  
Namasivayam Ambalavanan ◽  
Waldemar F. Carlo ◽  
Arlene Bulger ◽  
Jian Shi ◽  
Joseph B. Philips
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cigarette Smoke ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cigarette Smoke Extract

scholarly journals Cigarette smoke extract induces ferroptosis in vascular smooth muscle cells

2020 ◽  
Vol 318 (3) ◽  
pp. H508-H518 ◽  
Author(s):  
Ariunaa Sampilvanjil ◽  
Tadayoshi Karasawa ◽  
Naoya Yamada ◽  
Takanori Komada ◽  
Tsunehito Higashi ◽  
...  
Keyword(s):  
Cell Death ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cigarette Smoke ◽  
Vascular Smooth Muscle Cells ◽  
Ex Vivo ◽  
Muscle Cells ◽  
Iron Chelator ◽  
Cigarette Smoke Extract

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.

scholarly journals Cigarette Smoke Extract Causes Non-Apoptotic Cell Death in Neonatal Vascular Smooth Muscle Cells

1999 ◽  
Vol 45 (4, Part 2 of 2) ◽  
pp. 294A-294A
Author(s):  
Namasivayam Ambalavanan ◽  
Waldemar F Carlo ◽  
Arlene Bulger ◽  
Jian Shi ◽  
Joseph B Philips
Keyword(s):  
Cell Death ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cigarette Smoke ◽  
Vascular Smooth Muscle Cells ◽  
Apoptotic Cell ◽  
Muscle Cells ◽  
Cigarette Smoke Extract ◽  
Apoptotic Cell Death

Abstract 234: Cigarette Smoke Induction of Mmp9 in Aortic Vascular Smooth Muscle Cells is Mediated by the Jak/stat Pathway

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Abhijit Ghosh ◽  
Angela Pechota ◽  
Dawn Coleman ◽  
Gilbert R Upchurch ◽  
Jonathan L Eliason
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cigarette Smoke ◽  
Vascular Smooth Muscle Cells ◽  
Immunofluorescence Microscopy ◽  
Muscle Cells ◽  
Male Rat ◽  
Nuclear Fraction ◽  
Stat Pathway

Introduction Cigarette smoke has a strong correlation with abdominal aortic aneurysm (AAA) formation and is characterized by increased levels of MMP9 in the aorta. We hypothesized that smoke-induced MMP9 regulation is mediated by the Jak/Stat pathway thereby contributing to AAA formation. Methods Aqueous extract of cigarette smoke (AEC) was applied to male rat aortic vascular smooth muscle cells (RASMC) for 24 hours (h) in serum free medium (SFM), using SFM alone for controls. Media were collected for MMP2 and MMP9 zymography and proteins extracted from cells for phospho-Stat3 (pStat3), total Stat3 (T-Stat3), phospho-Jak2 (pJak2) and total Jak2 (T-Jak2) western blots. RASMC were transfected by siRNAs for Jak2 and Stat3 before AEC treatment to evaluate induction of MMPs. Coimmunoprecipitation and immunofluorescence microscopy investigated complex formation and cellular distribution of Jak2 and Stat3 following AEC treatment. Results MMP9 was increased in the medium of the AEC treated RASMC (P=0.005) and pro-MMP2 slightly elevated (P=0.055) at 24h compared to controls. By western blot protein extracts from AEC treated RASMC showed up regulation of pStat3, pJak2 and T-Jak2 and stable T-Stat3 compared with controls. siRNA transfection of RASMC for Jak2, Stat3 and a combination of Jak2 and Stat3 reduced MMP9 (P<0.005) and pro-MMP2 (P<0.05) in medium of AEC treated RASMC compared with AEC-treated cells transfected with control siRNA. Coimmunoprecipitation of total proteins from RASMC with total Jak2 antibody revealed increased levels of pStat3 in the AEC treated cells compared to controls, while separation of nuclear and cytoplasmic components followed by coimmunoprecipitation revealed more abundant Jak2/T-Stat3 complexes in the nuclear fraction than the cytoplasm following AEC treatment. Immunofluorescence microscopy revealed increased presence of pJak2, T-Jak2, pStat3 and T-Stat3 in the cytoplasm and nucleus of the AEC treated cells compared to the control cells. Conclusion This study suggests that cigarette smoke may result in AAA formation through Jak/Stat-mediated MMP9 production. siRNA inhibition of the Jak/Stat pathway greatly reduced AEC-induced MMP9 by RASMC and suggests a potential therapeutic target for the treatment of AAA.

NADPH oxidase (NOX) 1 mediates cigarette smoke-induced superoxide generation in rat vascular smooth muscle cells

2017 ◽  
Vol 38 ◽  
pp. 49-58 ◽  
Author(s):  
Kyung-Hwa Chang ◽  
Jung-Min Park ◽  
Chang Hoon Lee ◽  
Bumseok Kim ◽  
Kyung-Chul Choi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Nadph Oxidase ◽  
Smooth Muscle Cells ◽  
Cigarette Smoke ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Superoxide Generation
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