Mechanisms behind the atherothrombotic effects of acrolein, a review

Zirak, Mohammad Reza; Mehri, Soghra; Karimani, Asieh; Zeinali, Majid; Hayes, A. Wallace; Karimi, Gholamreza

doi:10.1016/j.fct.2019.04.034

Cited by 54 publications

(35 citation statements)

References 229 publications

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“…CSE and ACR can induce oxidative stress that contributes to endothelial dysfunction. 13) It has been reported that antioxidants such as GSH and N-acetyl-L-cysteine reduce the cytotoxicity of CSE and ACR. 5,13) Indeed, 300 μM GSH inhibited the 5% CSE-and 50 μM ACR-induced decreases in the phosphorylation and expression of eNOS (Fig.…”

Section: Effects Of Gsh On the Cse-and Acr-induced Changes In Phosphorylation And Expression Of Enos And Aktmentioning

confidence: 99%

“…Several studies have indicated that ACR is one of the substances present in high level in CSE. 3,4,13) We have reported that the concentration of ACR in the CSE, which was prepared by dissolving the gas phase of 10 cigarettes in 10 mL of water, was approximately 3.4 mM. 4) It means that the estimated amount of ACR generated is 3.4 μmol per one cigarette.…”

Section: Effects Of Gsh On the Cse-and Acr-induced Changes In Phosphorylation And Expression Of Enos And Aktmentioning

confidence: 99%

“…However, the action of ACR on endothelial cells remains controversial, because ACR causes endothelial cell injury and death, both of which contribute to endothelial dysfunction. 13,14) To clarify whether CSE and ACR are involved in endothelial dysfunction, this study examined their effects on human vascular endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

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Cigarette Smoke Extract and Its Cytotoxic Factor Acrolein Inhibit Nitric Oxide Production in Human Vascular Endothelial Cells

Horinouchi

Mazaki

Terada

et al. 2020

Biological & Pharmaceutical Bulletin

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Acrolein (ACR), a highly reactive α,β-unsaturated aldehyde, is a major cytotoxic factor in nicotine-and tar-free cigarette smoke extract (CSE). There are conflicting results regarding endothelial functions despite the fact that both CSE and ACR cause cellular damage. Several lines of evidence indicate that CSE impairs endothelium-derived nitric oxide (NO)-dependent vasodilation by reducing the activity and protein expression of endothelial NO synthase (eNOS), whereas ACR elicits endothelium-dependent vasorelaxation by increasing the production of NO and expression of eNOS. To clarify whether CSE and its cytotoxic factor ACR cause endothelial dysfunction, this study examined the effects of CSE and ACR on human vascular endothelial EA.hy926 cells. CSE and ACR reduced the phosphorylation of eNOS at Ser 1177 and total expression of eNOS. The CSE-and ACR-induced decrease in the phosphorylation and expression of eNOS was counteracted by glutathione (reduced form), an antioxidant. Basal NO production was inhibited by CSE, ACR, N G -nitro-L-arginine methyl ester (a competitive eNOS inhibitor), and nominally Ca 2+ -free solution supplemented with BAPTA-AM (a membrane permeable Ca 2+ chelator). These results indicate that CSE and ACR increase oxidative stress, and reduce NO production by reducing the activity and total protein level of eNOS.

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Section: Effects Of Gsh On the Cse-and Acr-induced Changes In Phosphorylation And Expression Of Enos And Aktmentioning

confidence: 99%

Section: Effects Of Gsh On the Cse-and Acr-induced Changes In Phosphorylation And Expression Of Enos And Aktmentioning

confidence: 99%

See 1 more Smart Citation

Cigarette Smoke Extract and Its Cytotoxic Factor Acrolein Inhibit Nitric Oxide Production in Human Vascular Endothelial Cells

Horinouchi

Mazaki

Terada

et al. 2020

Biological & Pharmaceutical Bulletin

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“…Acrolein, a highly active unsaturated aldehyde [15], is abundantly produced during the acute phase of TBI [16], and the strong covalent bonds to cellular and mitochondrial proteins can impair the structural and functional integrity in cells [17][18][19]. Other evidence also shows that acrolein is closely associated with the occurrence of thrombotic diseases [20], which indicates its role in stimulation of the coagulation cascade. Here, we hypothesized that acrolein promotes TBI-induced coagulopathy in the early stage.…”

Section: Introductionmentioning

confidence: 99%

Acrolein Induces Systemic Coagulopathy via Autophagy-dependent Secretion of von Willebrand Factor in Mice after Traumatic Brain Injury

Cui

Feng

et al. 2021

Neurosci. Bull.

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Traumatic brain injury (TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes, but the pathogenesis remains poorly understood. In this study, we aimed to investigate the causal role of acrolein, a typical lipid peroxidation product, in TBI-induced coagulopathy, and further explore the underlying molecular mechanisms. We found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without coagulopathy. Using a controlled cortical impact mouse model, we demonstrated that the acrolein scavenger phenelzine prevented TBI-induced coagulopathy and recombinant ADAMTS-13 prevented acrolein-induced coagulopathy by cleaving von Willebrand factor (VWF). Our results showed that acrolein may contribute to an early hypercoagulable state after TBI by regulating VWF secretion. mRNA sequencing (mRNA-seq) and transcriptome analysis indicated that acrolein over-activated autophagy, and subsequent experiments revealed that acrolein activated autophagy partly by regulating the Akt/mTOR pathway. In addition, we demonstrated that acrolein was produced in the perilesional cortex, affected endothelial cell integrity, and disrupted the blood-brain barrier. In conclusion, in this study we uncovered a novel pro-coagulant effect of acrolein that may contribute to TBI-induced coagulopathy and vascular leakage, providing an alternative therapeutic target.

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“…The toxic components present in the cigarette smoke are believed to pass through the blood vessels, damaging the blood vessel walls and causing cholesterol deposits. 6 …”

Section: Introductionmentioning

confidence: 99%

Curcumin Attenuates Acrolein-induced COX-2 Expression and Prostaglandin Production in Human Umbilical Vein Endothelial Cells

Lee

Park

Jeon

et al. 2020

J Lipid Atheroscler

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Objective Inflammation is crucial to limiting vascular disease. Previously we reported that acrolein, a known toxin in tobacco smoke, might play an important role in the progression of atherosclerosis via an inflammatory response involving cyclooxygenase-2 (COX-2) and prostaglandin production in human umbilical vein endothelial cells (HUVECs). Curcumin has been known to improve vascular function and have anti-inflammatory properties. In this study, we investigated whether curcumin prevents the induction of inflammatory response caused by acrolein. Methods Anti-inflammatory effects of curcumin were examined in acrolein-stimulated HUVECs. Induction of proteins, mRNA, prostaglandin and reactive oxygen species (ROS) were measured using immunoblot analysis, real-time reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay and flow cytometry, respectively. Results Curcumin attenuates inflammatory response via inhibition of COX-2 expression and prostaglandin production in acrolein-induced human endothelial cells. This inhibition by curcumin results in the abolition of phosphorylation of protein kinase C, p38 mitogen-activated protein kinase, and cAMP response element-binding protein. Furthermore, curcumin suppresses the production of ROS and endoplasmic reticulum stress via phosphorylation of eukaryotic initiation factor-2α caused by acrolein. Conclusion These results suggest that curcumin might be a useful agent against endothelial dysfunction caused by acrolein-induced inflammatory response.

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Mechanisms behind the atherothrombotic effects of acrolein, a review

Cited by 54 publications

References 229 publications

Cigarette Smoke Extract and Its Cytotoxic Factor Acrolein Inhibit Nitric Oxide Production in Human Vascular Endothelial Cells

Cigarette Smoke Extract and Its Cytotoxic Factor Acrolein Inhibit Nitric Oxide Production in Human Vascular Endothelial Cells

Acrolein Induces Systemic Coagulopathy via Autophagy-dependent Secretion of von Willebrand Factor in Mice after Traumatic Brain Injury

Curcumin Attenuates Acrolein-induced COX-2 Expression and Prostaglandin Production in Human Umbilical Vein Endothelial Cells

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