Flavored and Nicotine-Containing E-Cigarettes Induce Impaired Angiogenesis and Diabetic Wound Healing via Increased Endothelial Oxidative Stress and Reduced NO Bioavailability
The prevalent use of electronic cigarettes (e-cigarettes) has increased exponentially in recent years, especially in youth who are attracted to flavored e-cigarettes. Indeed, e-cigarette or vaping product use-associated lung injury (EVALI) cases started to emerge in the United States in August 2019,...
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MDPI AG
2022-05-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/5/904 |
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| author | Zhuoying Liu Yixuan Zhang Ji Youn Youn Yabing Zhang Ayako Makino Jason X.-J. Yuan Hua Cai |
| author_facet | Zhuoying Liu Yixuan Zhang Ji Youn Youn Yabing Zhang Ayako Makino Jason X.-J. Yuan Hua Cai |
| author_sort | Zhuoying Liu |
| collection | DOAJ |
| description | The prevalent use of electronic cigarettes (e-cigarettes) has increased exponentially in recent years, especially in youth who are attracted to flavored e-cigarettes. Indeed, e-cigarette or vaping product use-associated lung injury (EVALI) cases started to emerge in the United States in August 2019, resulting in 2807 hospitalized cases and 68 deaths as of 18 February 2020. In the present study, we investigated, for the first time, whether flavored and nicotine containing e-cigarettes induce endothelial dysfunction to result in impaired angiogenesis and wound healing particularly under diabetic condition. Nicotine containing e-cigarettes with various contents of nicotine (0, 1.2%, 2.4%), and flavored e-cigarettes of classic tobacco, mint, menthol, and vanilla or fruit from BLU (nicotine 2.4%) or JUUL (nicotine 3%), were used to treat endothelial cells in vitro and streptozotocin-induced diabetic mice in vivo. Endothelial cell superoxide production, determined by dihydroethidium (DHE) fluorescent imaging and electron spin resonance (ESR), was markedly increased by exposure to e-cigarette extract (e-CSE) in a nicotine-content dependent manner, while nitric oxide (NO) bioavailability detected by DAF-FM fluorescent imaging was substantially decreased. All of the different flavored e-cigarettes examined also showed significant effects in increasing superoxide production while diminishing NO bioavailability. Endothelial cell apoptosis evaluated by caspase 3 activity was markedly increased by exposure to e-CSE prepared from flavored and nicotine containing e-cigarettes. Endothelial monolayer wound assays revealed that nicotine-containing and flavored e-cigarettes induced impaired angiogenic wound repair of endothelial cell monolayers. Furthermore, vascular endothelial growth factor (VEGF) stimulated wound healing in diabetic mice was impaired by exposure to e-CSEs prepared from nicotine-containing and flavored e-cigarettes. Taken together, our data demonstrate for the first time that flavored and nicotine-containing e-cigarettes induce endothelial dysfunction through excessive ROS production, resulting in decreased NO bioavailability, increased endothelial cell apoptosis, and impairment in angiogenesis and wound healing, especially under diabetic condition. These responses of endothelial dysfunction likely underlie harmful effects of e-cigarettes in endothelial-rich organs, such as heart and lungs. These data also indicate that rigorous regulation on e-cigarette use should be enforced in diabetic and/or surgical patients to avoid severe consequences from impaired angiogenesis/wound healing. |
| first_indexed | 2024-03-10T03:25:57Z |
| format | Article |
| id | doaj.art-0153527efa904585a62ebc97c422127d |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T03:25:57Z |
| publishDate | 2022-05-01 |
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| series | Antioxidants |
| spelling | doaj.art-0153527efa904585a62ebc97c422127d2023-11-23T09:51:30ZengMDPI AGAntioxidants2076-39212022-05-0111590410.3390/antiox11050904Flavored and Nicotine-Containing E-Cigarettes Induce Impaired Angiogenesis and Diabetic Wound Healing via Increased Endothelial Oxidative Stress and Reduced NO BioavailabilityZhuoying Liu0Yixuan Zhang1Ji Youn Youn2Yabing Zhang3Ayako Makino4Jason X.-J. Yuan5Hua Cai6Department of Anesthesiology, Department of Medicine/Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USADepartment of Anesthesiology, Department of Medicine/Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USADepartment of Anesthesiology, Department of Medicine/Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USADepartment of Anesthesiology, Department of Medicine/Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USADepartment of Medicine, University of California San Diego, San Diego, CA 92093, USADepartment of Medicine, University of California San Diego, San Diego, CA 92093, USADepartment of Anesthesiology, Department of Medicine/Cardiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USAThe prevalent use of electronic cigarettes (e-cigarettes) has increased exponentially in recent years, especially in youth who are attracted to flavored e-cigarettes. Indeed, e-cigarette or vaping product use-associated lung injury (EVALI) cases started to emerge in the United States in August 2019, resulting in 2807 hospitalized cases and 68 deaths as of 18 February 2020. In the present study, we investigated, for the first time, whether flavored and nicotine containing e-cigarettes induce endothelial dysfunction to result in impaired angiogenesis and wound healing particularly under diabetic condition. Nicotine containing e-cigarettes with various contents of nicotine (0, 1.2%, 2.4%), and flavored e-cigarettes of classic tobacco, mint, menthol, and vanilla or fruit from BLU (nicotine 2.4%) or JUUL (nicotine 3%), were used to treat endothelial cells in vitro and streptozotocin-induced diabetic mice in vivo. Endothelial cell superoxide production, determined by dihydroethidium (DHE) fluorescent imaging and electron spin resonance (ESR), was markedly increased by exposure to e-cigarette extract (e-CSE) in a nicotine-content dependent manner, while nitric oxide (NO) bioavailability detected by DAF-FM fluorescent imaging was substantially decreased. All of the different flavored e-cigarettes examined also showed significant effects in increasing superoxide production while diminishing NO bioavailability. Endothelial cell apoptosis evaluated by caspase 3 activity was markedly increased by exposure to e-CSE prepared from flavored and nicotine containing e-cigarettes. Endothelial monolayer wound assays revealed that nicotine-containing and flavored e-cigarettes induced impaired angiogenic wound repair of endothelial cell monolayers. Furthermore, vascular endothelial growth factor (VEGF) stimulated wound healing in diabetic mice was impaired by exposure to e-CSEs prepared from nicotine-containing and flavored e-cigarettes. Taken together, our data demonstrate for the first time that flavored and nicotine-containing e-cigarettes induce endothelial dysfunction through excessive ROS production, resulting in decreased NO bioavailability, increased endothelial cell apoptosis, and impairment in angiogenesis and wound healing, especially under diabetic condition. These responses of endothelial dysfunction likely underlie harmful effects of e-cigarettes in endothelial-rich organs, such as heart and lungs. These data also indicate that rigorous regulation on e-cigarette use should be enforced in diabetic and/or surgical patients to avoid severe consequences from impaired angiogenesis/wound healing.https://www.mdpi.com/2076-3921/11/5/904e-cigarettes (nicotine containing and flavored)endothelial dysfunctionoxidative stressnitric oxide (NO) deficiencyapoptosisangiogenesis |
| spellingShingle | Zhuoying Liu Yixuan Zhang Ji Youn Youn Yabing Zhang Ayako Makino Jason X.-J. Yuan Hua Cai Flavored and Nicotine-Containing E-Cigarettes Induce Impaired Angiogenesis and Diabetic Wound Healing via Increased Endothelial Oxidative Stress and Reduced NO Bioavailability Antioxidants e-cigarettes (nicotine containing and flavored) endothelial dysfunction oxidative stress nitric oxide (NO) deficiency apoptosis angiogenesis |
| title | Flavored and Nicotine-Containing E-Cigarettes Induce Impaired Angiogenesis and Diabetic Wound Healing via Increased Endothelial Oxidative Stress and Reduced NO Bioavailability |
| title_full | Flavored and Nicotine-Containing E-Cigarettes Induce Impaired Angiogenesis and Diabetic Wound Healing via Increased Endothelial Oxidative Stress and Reduced NO Bioavailability |
| title_fullStr | Flavored and Nicotine-Containing E-Cigarettes Induce Impaired Angiogenesis and Diabetic Wound Healing via Increased Endothelial Oxidative Stress and Reduced NO Bioavailability |
| title_full_unstemmed | Flavored and Nicotine-Containing E-Cigarettes Induce Impaired Angiogenesis and Diabetic Wound Healing via Increased Endothelial Oxidative Stress and Reduced NO Bioavailability |
| title_short | Flavored and Nicotine-Containing E-Cigarettes Induce Impaired Angiogenesis and Diabetic Wound Healing via Increased Endothelial Oxidative Stress and Reduced NO Bioavailability |
| title_sort | flavored and nicotine containing e cigarettes induce impaired angiogenesis and diabetic wound healing via increased endothelial oxidative stress and reduced no bioavailability |
| topic | e-cigarettes (nicotine containing and flavored) endothelial dysfunction oxidative stress nitric oxide (NO) deficiency apoptosis angiogenesis |
| url | https://www.mdpi.com/2076-3921/11/5/904 |
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