alexa Homocysteine induces VCAM-1 gene expression through NF-kappaB and NAD(P)H oxidase activation: protective role of Mediterranean diet polyphenolic antioxidants.
Cardiology

Cardiology

Journal of Clinical & Experimental Cardiology

Author(s): Carluccio MA, Ancora MA, Massaro M, Carluccio M, Scoditti E,

Abstract Share this page

Abstract Hyperhomocysteinemia is a recognized risk factor for vascular disease, but pathogenetic mechanisms involved in its vascular actions are largely unknown. Because VCAM-1 expression is crucial in monocyte adhesion and early atherogenesis, we evaluated the NF-kappaB-related induction of VCAM-1 by homocysteine (Hcy) and the possible inhibitory effect of dietary polyphenolic antioxidants, such as trans-resveratrol (RSV) and hydroxytyrosol (HT), which are known inhibitors of NF-kappaB-mediated VCAM-1 induction. In human umbilical vein endothelial cells (HUVEC), Hcy, at 100 micromol/l, but not cysteine, induced VCAM-1 expression at the protein and mRNA levels, as shown by enzyme immunoassay and Northern analysis, respectively. Transfection studies with deletional VCAM-1 promoter constructs demonstrated that the two tandem NF-kappaB motifs in the VCAM-1 promoter are necessary for Hcy-induced VCAM-1 gene expression. Hcy-induced NF-kappaB activation was confirmed by EMSA, as shown by the nuclear translocation of its p65 (RelA) subunit and the degradation of the inhibitors IkappaB-alpha and IkappaB-beta by Western analysis. Hcy also increased intracellular reactive oxygen species by NAD(P)H oxidase activation, as shown by the membrane translocation of its p47(phox) subunit. NF-kappaB inhibitors decreased Hcy-induced intracellular reactive oxygen species and VCAM-1 expression. Finally, we found that nutritionally relevant concentrations of RSV and HT, but not folate and vitamin B6, reduce (by >60\% at 10(-6) mol/l) Hcy-induced VCAM-1 expression and monocytoid cell adhesion to the endothelium. These data indicate that pathophysiologically relevant Hcy concentrations induce VCAM-1 expression through a prooxidant mechanism involving NF-kappaB. Natural Mediterranean diet antioxidants can inhibit such activation, suggesting their possible therapeutic role in Hcy-induced vascular damage. This article was published in Am J Physiol Heart Circ Physiol and referenced in Journal of Clinical & Experimental Cardiology

Relevant Expert PPTs

Relevant Speaker PPTs

  • Donald silverberg
    Is correction of iron deficiency a new addition to the treatment of heart failure?
    PPT Version | PDF Version
  • Ahmed Zeidan
    Effects of intravenous iron in chronic kidney disease and heart failure
    PPT Version | PDF Version
  • Ming-Yow Hung
    Innate immunity in cardiology: Vessel and valve
    PPT Version | PDF Version
  • Yosef Yarden
    Classically, the 3’untranslated region (3’UTR) is that region in eukaryotic protein-coding genes from the translation termination codon to the polyA signal. It is transcribed as an integral part of the mRNA encoded by the gene. However, there exists another kind of RNA, which consists of the 3’UTR alone, without all other elements in mRNA such as 5’UTR and coding region. The importance of independent 3’UTR RNA (referred as I3’UTR) was prompted by results of artificially introducing such RNA species into malignant mammalian cells. Since 1991, we found that the middle part of the 3’UTR of the human nuclear factor for interleukin-6 (NF-IL6) or C/EBP gene exerted tumor suppression effect in vivo. Our subsequent studies showed that transfection of C/EBP 3’UTR led to down-regulation of several genes favorable for malignancy and to up-regulation of some genes favorable for phenotypic reversion. Also, it was shown that the sequences near the termini of the C/EBP 3’UTR were important for its tumor suppression activity. Then, the C/EBP 3’UTR was found to directly inhibit the phosphorylation activity of protein kinase CPKC in SMMC-7721, a hepatocarcinoma cell line. Recently, an AU-rich region in the C/EBP 3’UTR was found also to be responsible for its tumor suppression. Recently we have also found evidence that the independent C/EBP 3’UTR RNA is actually exists in human tissues, such as fetal liver and heart, pregnant uterus, senescent fibroblasts etc. Through 1990’s to 2000’s, world scientists found several 3’UTR RNAs that functioned as artificial independent RNAs in cancer cells and resulted in tumor suppression. Interestingly, majority of genes for these RNAs have promoter-like structures in their 3’UTR regions, although the existence of their transcribed products as independent 3’UTR RNAs is still to be confirmed. Our studies indicate that the independent 3’UTR RNA is a novel non-coding RNA species whose function should be the regulation not of the expression of their original mRNA, but of some essential life activities of the cell as a whole.
    PPT Version | PDF Version
  • Pupalan Iyngkaran
    Region Specific Cardiology Perspectives on the Cardiorenal Syndrome – Challenges and Solutions
    PPT Version | PDF Version
  • Ishfaq A Bukhari
    Protective Effect of Diltiazem and Fenofibrate Against Ischemia-reperfusion Induced Cardiac Arrhythmias in the Isolated Rat Heart.
    PPT Version | PDF Version
  • Manuela Stoicescu
    THE RISK OF COARCTATION OF THE AORTA IN PREGNANCY ORIGINAL CASE REPORT
    PDF Version
  • Hongxin Zhu
    UVRAG and Rubicon Regulate Cardiac Autophagy and Function
    PPT Version | PDF Version
  • Tamer M. A. Mohamed
    Targeting calcium signaling as a novel therapeutic strategy for cardiac hypertrophy and failure
    PDF Version
  • Monica V Marquezini
    Genotoxic risk for workers from São Paulo city, Brazil, due to occupational exposure to traffic air pollution
    PDF Version
  • M. Rizwan Sohail
    Cardiac Device Infections
    PDF Version
  • Renuka R. Nair
    RELATIONSHIP BETWEEN OXIDATIVE STRESS AND ENERGY METABOLISM IN HYPERTENSION INDUCED CARDIAC REMODELING
    PDF Version
  • A Martin Gerdes
    Wrong about β-blockers! Wrong about positive inotropes! Wrong about Thyroid Hormone treatment of Heart Failure?
    PDF Version
  • Galya Naydenova Atanasova
    Pulse pressure and apolipoprotein B/Apolipoprotein A1 in relation to the metabolic syndrome and its components
    PPT Version | PDF Version
  • Murad H. Al-Salamat
    Design of small synthetic molecules that mimic IL-4 binding to IL-4Rα, which therefore promotes alternate macrophage differentiation (M2) with minimal effect on the endothelial and vascular IL-4Rα.
    PDF Version

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords