The Protective Role of Bioactive Quinones in Stress-induced Senescence Phenotype of Endothelial Cells Exposed to Cigarette Smoke Extract
Open accessAbstract
Endothelial dysfunction represents the initial stage in atherosclerotic lesion development which occurs physiologically during aging, but external factors like diet, sedentary lifestyle, smoking accelerate it. Since cigarette smoking promotes oxidative stress and cell damage, we developed an in vitro model of endothelial dysfunction using vascular cells exposed to chemicals present in cigarette smoke, to help elucidate the protective effects of anti-inflammatory and antioxidant agents, such as ubiquinol and vitamin K, that play a fundamental role in vascular health. Treatment of both young and senescent Human Umbilical Vein Endothelial Cells (HUVECs) for 24 h with cigarette smoke extract (CSE) decreased cellular viability, induced apoptosis via reactive oxygen species (ROS) imbalance and mitochondrial dysfunction and promoted an inflammatory response. Moreover, the senescence marker SA-β-galactosidase was observed in both young CSE-exposed and in senescent HUVECs suggesting that CSE exposure accelerates aging in endothelial cells. Supplementation with 10 µM ubiquinol and menaquinone-7 (MK7) counteracted oxidative stress and inflammation, resulting in improved viability, decreased apoptosis and reduced SA-β-galactosidase, but were ineffective against CSE-induced mitochondrial permeability transition pore opening. Other K vitamins tested like menaquinone-4 (MK4) and menaquinone-1 (K1) were less protective. In conclusion, CSE exposure was able to promote a stress-induced senescent phenotype in young endothelial cells likely contributing to endothelial dysfunction in vivo. Furthermore, the molecular changes encountered could be offset by ubiquinol and menaquinone-7 supplementation, the latter resulting the most bioactive K vitamin in counteracting CSE-induced damage.
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Diminished inflammation, OS-induced senescence and apoptosis have been observed in HUVEC with CoQ10H2 in other studies.
“Diminished inflammation, OS-induced senescence and apoptosis have also been observed in the same cell line in other studies [69,72].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [72]
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- Authors
- Cirilli, I., Orlando, P., Marcheggiani, F., Dludla, P. V., Silvestri, S., Damiani, E., & Tiano, L.
- Affiliations
- Marche Polytechnic University (IT)
- South African Medical Research Council (ZA)
- Corresponding author
- Silvestri, Sonia
- Damiani, Elisabetta
- ORCID
- Venue
- Antioxidants
- Publisher
- MDPI AG
- Published
- 2020-10-16
- Volume
- 9
- Issue
- 10
- Pages
- 1008
- ISSN
- 2076-3921 (ISSN-L)
- PMC
- PMC7602940
- OpenAlex
- W3093068821
- Cited by
- 23
- References
- 59
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 8
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Antioxidants (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Polytechnic University of the Marche (Ricerca Scientifica di Ateneo (Luca Tiano))
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin K Research Studies
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- cigarette smoke extract, endothelial cell senescence, endothelial dysfunction, human umbilical vein endothelial cells, ubiquinol, menaquinone-7, vitamin K, oxidative stress, apoptosis, mitochondrial dysfunction, mitochondrial permeability transition pore, reactive oxygen species, inflammation, SA-β-galactosidase, atherosclerosis, aging
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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