ArticleArteriosclerosis, thrombosis, and vascular biology2018
Cigarette Smoke Initiates Oxidative Stress-Induced Cellular Phenotypic Modulation Leading to Cerebral Aneurysm Pathogenesis.
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Article in Arteriosclerosis, thrombosis, and vascular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 4 of them syntheses that pooled it.
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45citing papers in PubMed, 4 pooled it
3.9field-weighted citation impact, top 6% of its field
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Who cites it
45 citing papers in PubMed, 4 syntheses or guidelines pooled it, 81 citations in OpenAlex.
- Analysis of aneurysmal subarachnoid hemorrhage as a multistep process.European journal of neurology · 2024Pooled it
- The Role of NF-κB in Intracranial Aneurysm Pathogenesis: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Animal model contributes to the development of intracranial aneurysm: A bibliometric analysis.Frontiers in veterinary science · 2022Pooled it
- Extreme Diversity of the Human Vascular Mesenchymal Cell Landscape.Journal of the American Heart Association · 2020Pooled it
- Glycation and Oxidative Stress Increase Autoantibodies in the Elderly.Molecules (Basel, Switzerland) · 2020Trial
- Nicotine-containing products and the cardiovascular system: mechanisms and global health implications.Nature reviews. Cardiology · 2026Review
- HMGB1 promotes intracranial aneurysm progression by regulating vascular smooth muscle cell phenotypic switching and ferroptosis.Journal of molecular histology · 2026Article
- Subarachnoid hemorrhage: epidemiology, risk factors, pathogenesis, and clinical therapies.Molecular biomedicine · 2026Review
- Recreational substance use and aneurysmal subarachnoid hemorrhage: differential effects of alcohol and THC.Neurosurgical review · 2026Article
- Machine learning predicts severe adverse events and salvage success of CT-guided lung biopsy after nondiagnostic transbronchial lung biopsy.European radiology · 2026Article
- Cerebral vascular tortuosity and aneurysm formation and rupture: a novel vessel tortuosity scale.Experimental neurology · 2026Article
- From genes to diagnosis: The impact of UNC5B and DOK5 in intracranial aneurysm detection and pathogenesis.PloS one · 2026Article
- The Convergent Immunopathogenesis of Cigarette Smoke Exposure: From Oxidative Stress to Epigenetic Reprogramming in Chronic Disease.International journal of molecular sciences · 2025Review
- Overstretch causes lipid accumulation in vascular smooth muscle cells dependent on NADPH oxidase 1.Mechanobiology in medicine · 2025Article
- Tobacco cigarette smoking induces cerebrovascular dysfunction followed by oxidative neuronal injury with the onset of cognitive impairment.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025Article
- Current Mouse Models of Intracranial Aneurysms: Analysis of Pharmacological Agents Used to Induce Aneurysms and Their Impact on Translational Research.Journal of the American Heart Association · 2024Review
- Cigarette Smoke-Induced Reactive Oxygen Species Formation: A Concise Review.Antioxidants (Basel, Switzerland) · 2023Review
- An integral perspective of canonical cigarette and e-cigarette-related cardiovascular toxicity based on the adverse outcome pathway framework.Journal of advanced research · 2023Review
- Smooth Muscle Cell Phenotypic Switch Induced by Traditional Cigarette Smoke Condensate: A Holistic Overview.International journal of molecular sciences · 2023Article
- The Involvement of Krüppel-like Factors in Cardiovascular Diseases.Life (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Robert M StarkeFrom the Department of Neurological Surgery & Radiology, University of Miami Cerebrovascular Initiative (R.M.S., J.W.T.), Department of Biochemistry and Molecular Biology (M.T.), and Department of Cardiology and Molecular and Cellular Pharmacology (J.M.H.), University of Miami, FL; Department of Neurosurgery, University of Iowa, Iowa City (M.S.A., D.M.H.); Department of Neurological Surgery, Tulane University, New Orleans, LA (C.L.P., A.M.L., A.S.D.); Department of Neurosurgery (D.D.) and Department of Molecular Physiology & Biophysics, Robert M. Berne Cardiovascular Research Center (G.K.O.), University of Virginia, Charlottesville; and Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA (N.C., P.J.). RStarke@med.miami.edu.
John W ThompsonFrom the Department of Neurological Surgery & Radiology, University of Miami Cerebrovascular Initiative (R.M.S., J.W.T.), Department of Biochemistry and Molecular Biology (M.T.), and Department of Cardiology and Molecular and Cellular Pharmacology (J.M.H.), University of Miami, FL; Department of Neurosurgery, University of Iowa, Iowa City (M.S.A., D.M.H.); Department of Neurological Surgery, Tulane University, New Orleans, LA (C.L.P., A.M.L., A.S.D.); Department of Neurosurgery (D.D.) and Department of Molecular Physiology & Biophysics, Robert M. Berne Cardiovascular Research Center (G.K.O.), University of Virginia, Charlottesville; and Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA (N.C., P.J.).
Muhammad S AliFrom the Department of Neurological Surgery & Radiology, University of Miami Cerebrovascular Initiative (R.M.S., J.W.T.), Department of Biochemistry and Molecular Biology (M.T.), and Department of Cardiology and Molecular and Cellular Pharmacology (J.M.H.), University of Miami, FL; Department of Neurosurgery, University of Iowa, Iowa City (M.S.A., D.M.H.); Department of Neurological Surgery, Tulane University, New Orleans, LA (C.L.P., A.M.L., A.S.D.); Department of Neurosurgery (D.D.) and Department of Molecular Physiology & Biophysics, Robert M. Berne Cardiovascular Research Center (G.K.O.), University of Virginia, Charlottesville; and Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA (N.C., P.J.).
Crissey L PascaleFrom the Department of Neurological Surgery & Radiology, University of Miami Cerebrovascular Initiative (R.M.S., J.W.T.), Department of Biochemistry and Molecular Biology (M.T.), and Department of Cardiology and Molecular and Cellular Pharmacology (J.M.H.), University of Miami, FL; Department of Neurosurgery, University of Iowa, Iowa City (M.S.A., D.M.H.); Department of Neurological Surgery, Tulane University, New Orleans, LA (C.L.P., A.M.L., A.S.D.); Department of Neurosurgery (D.D.) and Department of Molecular Physiology & Biophysics, Robert M. Berne Cardiovascular Research Center (G.K.O.), University of Virginia, Charlottesville; and Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA (N.C., P.J.).
Alejandra Martinez LegeFrom the Department of Neurological Surgery & Radiology, University of Miami Cerebrovascular Initiative (R.M.S., J.W.T.), Department of Biochemistry and Molecular Biology (M.T.), and Department of Cardiology and Molecular and Cellular Pharmacology (J.M.H.), University of Miami, FL; Department of Neurosurgery, University of Iowa, Iowa City (M.S.A., D.M.H.); Department of Neurological Surgery, Tulane University, New Orleans, LA (C.L.P., A.M.L., A.S.D.); Department of Neurosurgery (D.D.) and Department of Molecular Physiology & Biophysics, Robert M. Berne Cardiovascular Research Center (G.K.O.), University of Virginia, Charlottesville; and Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA (N.C., P.J.).
Dale DingFrom the Department of Neurological Surgery & Radiology, University of Miami Cerebrovascular Initiative (R.M.S., J.W.T.), Department of Biochemistry and Molecular Biology (M.T.), and Department of Cardiology and Molecular and Cellular Pharmacology (J.M.H.), University of Miami, FL; Department of Neurosurgery, University of Iowa, Iowa City (M.S.A., D.M.H.); Department of Neurological Surgery, Tulane University, New Orleans, LA (C.L.P., A.M.L., A.S.D.); Department of Neurosurgery (D.D.) and Department of Molecular Physiology & Biophysics, Robert M. Berne Cardiovascular Research Center (G.K.O.), University of Virginia, Charlottesville; and Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA (N.C., P.J.).
Nohra ChalouhiFrom the Department of Neurological Surgery & Radiology, University of Miami Cerebrovascular Initiative (R.M.S., J.W.T.), Department of Biochemistry and Molecular Biology (M.T.), and Department of Cardiology and Molecular and Cellular Pharmacology (J.M.H.), University of Miami, FL; Department of Neurosurgery, University of Iowa, Iowa City (M.S.A., D.M.H.); Department of Neurological Surgery, Tulane University, New Orleans, LA (C.L.P., A.M.L., A.S.D.); Department of Neurosurgery (D.D.) and Department of Molecular Physiology & Biophysics, Robert M. Berne Cardiovascular Research Center (G.K.O.), University of Virginia, Charlottesville; and Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA (N.C., P.J.).
David M HasanFrom the Department of Neurological Surgery & Radiology, University of Miami Cerebrovascular Initiative (R.M.S., J.W.T.), Department of Biochemistry and Molecular Biology (M.T.), and Department of Cardiology and Molecular and Cellular Pharmacology (J.M.H.), University of Miami, FL; Department of Neurosurgery, University of Iowa, Iowa City (M.S.A., D.M.H.); Department of Neurological Surgery, Tulane University, New Orleans, LA (C.L.P., A.M.L., A.S.D.); Department of Neurosurgery (D.D.) and Department of Molecular Physiology & Biophysics, Robert M. Berne Cardiovascular Research Center (G.K.O.), University of Virginia, Charlottesville; and Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA (N.C., P.J.).
Pascal JabbourFrom the Department of Neurological Surgery & Radiology, University of Miami Cerebrovascular Initiative (R.M.S., J.W.T.), Department of Biochemistry and Molecular Biology (M.T.), and Department of Cardiology and Molecular and Cellular Pharmacology (J.M.H.), University of Miami, FL; Department of Neurosurgery, University of Iowa, Iowa City (M.S.A., D.M.H.); Department of Neurological Surgery, Tulane University, New Orleans, LA (C.L.P., A.M.L., A.S.D.); Department of Neurosurgery (D.D.) and Department of Molecular Physiology & Biophysics, Robert M. Berne Cardiovascular Research Center (G.K.O.), University of Virginia, Charlottesville; and Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA (N.C., P.J.).
Gary K OwensFrom the Department of Neurological Surgery & Radiology, University of Miami Cerebrovascular Initiative (R.M.S., J.W.T.), Department of Biochemistry and Molecular Biology (M.T.), and Department of Cardiology and Molecular and Cellular Pharmacology (J.M.H.), University of Miami, FL; Department of Neurosurgery, University of Iowa, Iowa City (M.S.A., D.M.H.); Department of Neurological Surgery, Tulane University, New Orleans, LA (C.L.P., A.M.L., A.S.D.); Department of Neurosurgery (D.D.) and Department of Molecular Physiology & Biophysics, Robert M. Berne Cardiovascular Research Center (G.K.O.), University of Virginia, Charlottesville; and Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA (N.C., P.J.).
Michal ToborekFrom the Department of Neurological Surgery & Radiology, University of Miami Cerebrovascular Initiative (R.M.S., J.W.T.), Department of Biochemistry and Molecular Biology (M.T.), and Department of Cardiology and Molecular and Cellular Pharmacology (J.M.H.), University of Miami, FL; Department of Neurosurgery, University of Iowa, Iowa City (M.S.A., D.M.H.); Department of Neurological Surgery, Tulane University, New Orleans, LA (C.L.P., A.M.L., A.S.D.); Department of Neurosurgery (D.D.) and Department of Molecular Physiology & Biophysics, Robert M. Berne Cardiovascular Research Center (G.K.O.), University of Virginia, Charlottesville; and Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA (N.C., P.J.).
Joshua M HareFrom the Department of Neurological Surgery & Radiology, University of Miami Cerebrovascular Initiative (R.M.S., J.W.T.), Department of Biochemistry and Molecular Biology (M.T.), and Department of Cardiology and Molecular and Cellular Pharmacology (J.M.H.), University of Miami, FL; Department of Neurosurgery, University of Iowa, Iowa City (M.S.A., D.M.H.); Department of Neurological Surgery, Tulane University, New Orleans, LA (C.L.P., A.M.L., A.S.D.); Department of Neurosurgery (D.D.) and Department of Molecular Physiology & Biophysics, Robert M. Berne Cardiovascular Research Center (G.K.O.), University of Virginia, Charlottesville; and Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA (N.C., P.J.).
Aaron S DumontFrom the Department of Neurological Surgery & Radiology, University of Miami Cerebrovascular Initiative (R.M.S., J.W.T.), Department of Biochemistry and Molecular Biology (M.T.), and Department of Cardiology and Molecular and Cellular Pharmacology (J.M.H.), University of Miami, FL; Department of Neurosurgery, University of Iowa, Iowa City (M.S.A., D.M.H.); Department of Neurological Surgery, Tulane University, New Orleans, LA (C.L.P., A.M.L., A.S.D.); Department of Neurosurgery (D.D.) and Department of Molecular Physiology & Biophysics, Robert M. Berne Cardiovascular Research Center (G.K.O.), University of Virginia, Charlottesville; and Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA (N.C., P.J.).
Tulane University · USUniversity of Iowa · USUniversity of Virginia · USNeurological Surgery · US
Funding
Cardioprotective Effect of Growth Hormone Releasing HormoneR01HL107110 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HARE, JOSHUA M · 2011 to 2020
$5.9MCell Based Therapy for Non-Ischemic Dilated CardiomyopathyUM1HL113460 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HARE, JOSHUA M · 2012 to 2018
$4.3MCellular Cardiomyoplasty for Chronic Heart FailureR01HL084275 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HARE, JOSHUA M · 2007 to 2016
$3.8MRole of OxPLs and Oct4 in SMC Phenotypic Switching in AtherosclerosisR01HL087867 · NHLBI · UNIVERSITY OF VIRGINIA · PI OWENS, GARY K · 2008 to 2016
$3.5MEpigenetic Control of Smooth Muscle Cell Lineage and Phenotypic SwitchingR01HL057353 · NHLBI · UNIVERSITY OF VIRGINIA · PI OWENS, GARY K · 2008 to 2016
$3.5MStem Cells for Dilated CardiomyopathyR01HL110737 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HARE, JOSHUA M · 2011 to 2015
$3.2MKLF4-Dependent Regulation of SMC Differentiation and Phenotypic SwitchingR01HL098538 · NHLBI · UNIVERSITY OF VIRGINIA · PI OWENS, GARY K · 2010 to 2013
$2.7MNitroso/redox balance in myocardial infarctionR01HL094849 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HARE, JOSHUA M · 2009 to 2013
$2.2MNitric Oxide and sex differences in cardiac repairR01HL137355 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI HARE, JOSHUA M · 2017 to 2020
$1.6MTNF-a and vascular smooth muscle cell phenotypic modulation in cerebral aneurysmsK08NS067072 · NINDS · UNIVERSITY OF VIRGINIA · PI DUMONT, AARON S · 2009 to 2013
$886kMechanisms of Effect of Aspirin on Cerebral Aneurysms in MiceK08NS082363 · NINDS · UNIVERSITY OF IOWA · PI HASAN, DAVID M. · 2013 to 2017
$846kAneurysm Sac Growth as the Etiology of Recurrence in Coiled Cerebral AneurysmsR03NS079227 · NINDS · UNIVERSITY OF IOWA · PI HASAN, DAVID M. · 2012 to 2013
$148kNHLBI NIH HHS R01 HL057353NHLBI NIH HHS R01 HL084275NHLBI NIH HHS R01 HL087867NHLBI NIH HHS R01 HL094849NHLBI NIH HHS R01 HL098538NHLBI NIH HHS R01 HL107110NHLBI NIH HHS R01 HL110737NHLBI NIH HHS R01 HL137355NHLBI NIH HHS UM1 HL113460NINDS NIH HHS K08 NS067072NINDS NIH HHS K08 NS082363NINDS NIH HHS R03 NS079227
Abstract
objectiveCigarette smoke exposure (CSE) is a risk factor for cerebral aneurysm (CA) formation, but the molecular mechanisms are unclear. Although CSE is known to contribute to excess reactive oxygen species generation, the role of oxidative stress on vascular smooth muscle cell (VSMC) phenotypic modulation and pathogenesis of CAs is unknown. The goal of this study was to investigate whether CSE activates a NOX (NADPH oxidase)-dependent pathway leading to VSMC phenotypic modulation and CA formation and rupture. APPROACH AND
resultsIn cultured cerebral VSMCs, CSE increased expression of NOX1 and reactive oxygen species which preceded upregulation of proinflammatory/matrix remodeling genes (MCP-1, MMPs [matrix metalloproteinase], TNF-α, IL-1β, NF-κB, KLF4 [Kruppel-like factor 4]) and downregulation of contractile genes (SM-α-actin [smooth muscle α actin], SM-22α [smooth muscle 22α], SM-MHC [smooth muscle myosin heavy chain]) and myocardin. Inhibition of reactive oxygen species production and knockdown of NOX1 with siRNA or antisense decreased CSE-induced upregulation of NOX1 and inflammatory genes and downregulation of VSMC contractile genes and myocardin. p47phox
conclusionsCSE initiates oxidative stress-induced phenotypic modulation of VSMCs and CA formation and rupture. These molecular changes implicate oxidative stress in the pathogenesis of CAs and may provide a potential target for future therapeutic strategies.
Indexed as
Oxidative StressSmokeAcetophenonesAneurysm, RupturedAnimalsAntioxidantsCells, CulturedCerebral ArteriesCigarette SmokingDilatation, PathologicDisease Models, AnimalIntracranial AneurysmKruppel-Like Factor 4MaleMice, KnockoutMuscle, Smooth, VascularAcetophenonesacetovanilloneAntioxidantsKlf4 protein, mouseKlf4 protein, ratKruppel-Like Factor 4NADPH Oxidase 1NADPH Oxidasesneutrophil cytosolic factor 1NOX1 protein, mouseNOX1 protein, ratSmokeaneurysmatherosclerosisoxygenrupturesmokesubarachnoid hemorrhage
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