Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Vascular incorporation of alpha-tocopherol prevents endothelial dysfunction due to oxidized LDL by inhibiting protein kinase C stimulation.
J F Keaney Jr, … , A Xu, J A Vita
J F Keaney Jr, … , A Xu, J A Vita
Published July 15, 1996
Citation Information: J Clin Invest. 1996;98(2):386-394. https://doi.org/10.1172/JCI118804.
View: Text | PDF
Research Article Article has an altmetric score of 2

Vascular incorporation of alpha-tocopherol prevents endothelial dysfunction due to oxidized LDL by inhibiting protein kinase C stimulation.

  • Text
  • PDF
Abstract

Excess vascular oxidative stress has been linked to impaired endothelium-dependent arterial relaxation in hypercholesterolemia. alpha-Tocopherol (AT) preserves endothelial function in hypercholesterolemia although the mechanism(s) for this protective effect is (are) not known. We examined the tissue-specific effects of AT on oxidized LDL (ox-LDL)-mediated endothelial dysfunction in male New Zealand White rabbits. Animals consumed chow deficient in (< 10 IU/kg) or supplemented with (1,000 IU/kg) AT for 28 d. Exposure of thoracic aortae from AT-deficient animals to ox-LDL (0-500 microg/ml) for 4 h produced dose-dependent inhibition of acetylcholine-mediated relaxation (P < 0.05) while vessels derived from animals consuming AT were resistant to ox-LDL-mediated endothelial dysfunction. Animals consuming AT demonstrated a 100-fold increase in vascular AT content and this was strongly correlated with vessel resistance to endothelial dysfunction from ox-LDL (R = 0.67; P = 0.0014). These results were not explained by an effect of AT on ox-LDL-mediated cytotoxicity by LDH assay or scanning electron microscopy. Vascular incorporation of AT did produce resistance to endothelial dysfunction from protein kinase C stimulation, an event that has been implicated in the vascular response to ox-LDL. Human aortic endothelial cells loaded with AT also demonstrated resistance to protein kinase C stimulation by both phorbol ester and ox-LDL. Thus, these data indicate that enrichment of vascular tissue with AT protects the vascular endothelium from ox-LDL-mediated dysfunction, at least in part, through the inhibition of protein kinase C stimulation. These findings suggest one potential mechanism for the observed beneficial effect of AT in preventing the clinical expression of coronary artery disease that is distinct from the antioxidant protection of LDL.

Authors

J F Keaney Jr, Y Guo, D Cunningham, G T Shwaery, A Xu, J A Vita

×

Total citations by year

Year: 2024 2022 2021 2020 2019 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1995 1994 Total
Citations: 1 1 1 1 2 1 2 3 1 3 2 5 4 10 2 7 13 11 5 16 21 14 17 9 3 1 1 157
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2005 (13)

Title and authors Publication Year
Cardioprotective mechanisms of Rho-kinase inhibition associated with eNOS and oxidative stress-LOX-1 pathway in Dahl salt-sensitive hypertensive rats
S Mita, N Kobayashi, K Yoshida, S Nakano, H Matsuoka
Journal of Hypertension 2005
Nitric oxide in coronary artery disease: effects of antioxidants
D Tousoulis, C Antoniades, C Stefanadis
European Journal of Clinical Pharmacology 2005
VITAMIN E, OXIDATIVE STRESS, AND INFLAMMATION
U Singh, S Devaraj, I Jialal
Annual Review of Nutrition 2005
Antioxidants and endothelium protection
D Praticò
Atherosclerosis 2005
Antioxidants and endothelial nitric oxide synthesis
R Heller, G Werner-Felmayer, ER Werner
European Journal of Clinical Pharmacology 2005
Effects of vitamin C on intracoronary L-arginine dependent coronary vasodilatation in patients with stable angina
D Tousoulis, C Xenakis, C Tentolouris, G Davies, C Antoniades, T Crake, C Stefanadis
Heart (British Cardiac Society) 2005
Local Drug Delivery for Coronary Artery Disease: Established and Emerging Applications
X Liu, ID Scheerder
Local Drug Delivery for Coronary Artery Disease: Established and Emerging Applications 2005
PRETREATMENT WITH INTRAVENOUS ASCORBIC ACID PRESERVES ENDOTHELIAL FUNCTION DURING ACUTE HYPERGLYCAEMIA (R1)
BA Mullan, CN Ennis, HJ Fee, IS Young, DR McCance
Clinical and experimental pharmacology & physiology 2005
Vitamin A deficiency induces prooxidant environment and inflammation in rat aorta
L Gatica, S Alvarez, N Gomez, MP Zago, P Oteiza, L Oliveros, MS Gimenez
Free Radical Research 2005
Influence of vitamin E on the antiplatelet effect of acetylsalicylic acid in human blood
JA González-Correa, MM Arrebola, A Guerrero, J Muñoz-Marín, D Ruiz-Villafranca, FS de la Cuesta, JP la Cruz
Platelets 2005
LDL-cholesterol predicts negative coronary artery remodelling in diabetic patients: an intravascular ultrasound study
P Jiménez-Quevedo, M Sabaté, D Angiolillo, F Alfonso, R Hernández-Antolín, C Bañuelos, E Bernardo, C Ramirez, R Moreno, C Fernández, J Escaned, C Macaya
European Heart Journal 2005
Cardioprotective Mechanisms of Spironolactone Associated with the Angiotensin-Converting Enzyme/Epidermal Growth Factor Receptor/Extracellular Signal-Regulated Kinases, NAD(P)H Oxidase/Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1, and Rho-Kinase Pathways in Aldosterone/Salt-Induced Hypertensive Rats
S NAKANO, N KOBAYASHI, K YOSHIDA, T OHNO, H MATSUOKA
Hypertension Research 2005
Alpha-tocopherol supplementation favorable effects on blood pressure, blood viscosity and cardiac remodeling of spontaneously hypertensive rats
VA Costa, LM Vianna, MB Aguila, CA Mandarim-de-Lacerda
The Journal of Nutritional Biochemistry 2005

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Posted by 2 X users
26 readers on Mendeley
See more details