ArticleCardiovascular research2022
Nicotine promotes vascular calcification via intracellular Ca2+-mediated, Nox5-induced oxidative stress, and extracellular vesicle release in vascular smooth muscle cells.
Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 92 citations in OpenAlex.
- Proteome-wide genetic analyses identify ASGR1 as a potential biomarker linking smoking with ischemic heart disease.Nature cardiovascular research · 2026Article
- Association Between Cigarette Smoking and Carotid Plaque Stiffness Assessed Using Ultrasound Shear-Wave Elastography.Tomography (Ann Arbor, Mich.) · 2026Article
- ALOX5-Mediated LTA4 Production Enhances PLCG2/IP3 Signaling and Exacerbates Calcification in Human Aortic Valve Interstitial Cells.Acta Cardiologica Sinica · 2026Article
- Nicotine-Mediated Redox and Nitrosative Stress in Cardiorenal Health.Hypertension (Dallas, Tex. : 1979) · 2026Review
- Nogo-B attenuates vascular calcification by activating NRF2-SLC7A11 to enhance antioxidant defense.Redox biology · 2026Article
- Sex-Specific Effects of Menaquinone-7 (MK-7) Supplementation on Body Composition and Adiposity Markers.Nutrients · 2026Article
- Curcumin mitigated aflatoxin BJournal of animal science and biotechnology · 2026Article
- Apolipoprotein C3 exacerbates vascular calcification by promoting ferroptosis via the TLR2/AMPK pathway in vascular smooth muscle cells.Redox biology · 2026Article
- PHGDH mediated serine biosynthesis metabolism suppresses vascular calcification.Biology direct · 2026Article
- Associations of cigarette smoking with coronary artery and extra-coronary calcification in older adults: The Atherosclerosis Risk in Communities study.Atherosclerosis · 2026Article
- Time to first cigarette after waking and incident heart failure: a dose-response analysis from the UK biobank.ESC heart failure · 2026Article
- Low dose thirdhand smoke exposure enhances platelet functional responses in mice.Experimental biology and medicine (Maywood, N.J.) · 2026Article
- Association of serum uric acid with incident vascular calcification in patients with type 2 diabetes mellitus: a retrospective cohort study.Frontiers in endocrinology · 2026Article
- Mechanisms of vascular calcification: cellular phenotype switching drives matrix remodeling and mineralized microenvironment formation.Frontiers in cardiovascular medicine · 2026Review
- Study on the effect of community intervention on patients with hypertension in high-normal blood pressure.Frontiers in medicine · 2026Article
- Targeting VSMCs to suppress macrophage-like phenotype switching that restrains atherogenesis by immunosuppressive oligodeoxynucleotide (A151) functionalized selenium nanoparticles.Journal of nanobiotechnology · 2025Article
- Development and validation of a nomogram model for predicting infarction after superficial temporal artery‒middle cerebral artery bypass in patients with intracranial atherosclerotic stenosis.Neurosurgical review · 2025Article
- Inhibition of long interspersed nuclear element-1 by nucleoside reverse transcriptase inhibitors attenuates vascular calcification.Signal transduction and targeted therapy · 2025Article
- Article
- The Non-Traditional Cardiovascular Culprits in Chronic Kidney Disease: Mineral Imbalance and Uremic Toxin Accumulation.International journal of molecular sciences · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsSmokers are at increased risk of cardiovascular events. However, the exact mechanisms through which smoking influences cardiovascular disease resulting in accelerated atherosclerosis and vascular calcification are unknown. The aim of this study was to investigate effects of nicotine on initiation of vascular smooth muscle cell (VSMC) calcification and to elucidate underlying mechanisms. METHODS AND
resultsWe assessed vascular calcification of 62 carotid lesions of both smoking and non-smoking patients using ex vivo micro-computed tomography (µCT) scanning. Calcification was present more often in carotid plaques of smokers (n = 22 of 30, 73.3%) compared to non-smokers (n = 11 of 32, 34.3%; P < 0.001), confirming higher atherosclerotic burden. The difference was particularly profound for microcalcifications, which was 17-fold higher in smokers compared to non-smokers. In vitro, nicotine-induced human primary VSMC calcification, and increased osteogenic gene expression (Runx2, Osx, BSP, and OPN) and extracellular vesicle (EV) secretion. The pro-calcifying effects of nicotine were mediated by Ca2+-dependent Nox5. SiRNA knock-down of Nox5 inhibited nicotine-induced EV release and calcification. Moreover, pre-treatment of hVSMCs with vitamin K2 ameliorated nicotine-induced intracellular oxidative stress, EV secretion, and calcification. Using nicotinic acetylcholine receptor (nAChR) blockers α-bungarotoxin and hexamethonium bromide, we found that the effects of nicotine on intracellular Ca2+ and oxidative stress were mediated by α7 and α3 nAChR. Finally, we showed that Nox5 expression was higher in carotid arteries of smokers and correlated with calcification levels in these vessels.
conclusionIn this study, we provide evidence that nicotine induces Nox5-mediated pro-calcific processes as novel mechanism of increased atherosclerotic calcification. We identified that activation of α7 and α3 nAChR by nicotine increases intracellular Ca2+ and initiates calcification of hVSMCs through increased Nox5 activity, leading to oxidative stress-mediated EV release. Identifying the role of Nox5-induced oxidative stress opens novel avenues for diagnosis and treatment of smoking-induced cardiovascular disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.