title: Caffeic acid, a phenol found in white wine, modulates endothelial nitric oxide production and protects from oxidative stress-associated endothelial cell injury.
abstract: BACKGROUND
  Several studies demonstrated that endothelium dependent vasodilatation is impaired in cardiovascular and chronic kidney diseases because of oxidant stress-induced nitric oxide availability reduction. The Mediterranean diet, which is characterized by food containing phenols, was correlated with a reduced incidence of cardiovascular diseases and delayed progression toward end stage chronic renal failure. Previous studies demonstrated that both red and white wine exert cardioprotective effects. In particular, wine contains Caffeic acid (CAF), an active component with known antioxidant activities.
  
  
  OBJECTIVE
  The aim of the present study was to investigate the protective effect of low doses of CAF on oxidative stress-induced endothelial injury.
  
  
  RESULTS
  CAF increased basal as well as acetylcholine-induced NO release by a mechanism independent from eNOS expression and phosphorylation. In addition, low doses of CAF (100 nM and 1 μM) increased proliferation and angiogenesis and inhibited leukocyte adhesion and endothelial cell apoptosis induced by hypoxia or by the uremic toxins ADMA, p-cresyl sulfate and indoxyl sulfate. The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production. In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.
  
  
  CONCLUSIONS
  The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation. CAF-induced NO modulation may limit cardiovascular and kidney disease progression associated with oxidative stress-mediated endothelial injury.
authors: Nephrology and Dialysis Unit, Versilia Hospital, Lido di Camaiore, Italy.
authors: Massimiliano
authors: M
authors: Migliori
authors: Nephrology, Dialysis and Kidney Transplantation Unit, Department of Medical Sciences, University of Torino, Torino, Italy.
authors: Vincenzo
authors: V
authors: Cantaluppi
authors: Department of Translational Research and New Technology in Medicine, University of Pisa, Pisa, Italy.
authors: Claudio
authors: C
authors: Mannari
authors: Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
authors: Alberto A E
authors: AA
authors: Bertelli
authors: Nephrology, Dialysis and Kidney Transplantation Unit, Department of Medical Sciences, University of Torino, Torino, Italy.
authors: Davide
authors: D
authors: Medica
authors: Nephrology, Dialysis and Kidney Transplantation Unit, Department of Medical Sciences, University of Torino, Torino, Italy.
authors: Alessandro Domenico
authors: AD
authors: Quercia
authors: Nephrology, Dialysis and Kidney Transplantation Unit, Department of Medical Sciences, University of Torino, Torino, Italy.
authors: Victor
authors: V
authors: Navarro
authors: Nephrology and Dialysis Unit, Versilia Hospital, Lido di Camaiore, Italy.
authors: Alessia
authors: A
authors: Scatena
authors: Department of Translational Research and New Technology in Medicine, University of Pisa, Pisa, Italy.
authors: Luca
authors: L
authors: Giovannini
authors: Nephrology, Dialysis and Kidney Transplantation Unit, Department of Medical Sciences, University of Torino, Torino, Italy.
authors: Luigi
authors: L
authors: Biancone
authors: Nephrology and Dialysis Unit, Versilia Hospital, Lido di Camaiore, Italy.
authors: Vincenzo
authors: V
authors: Panichi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002109:Caffeic Acids / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006098:Granulocytes / Q000276:immunology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects / Q000276:immunology / Q000293:injuries; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014511:Uremia / Q000378:metabolism / Q000473:pathology; D014920:Wine / Q000032:analysis*
chemical_list: D000975:Antioxidants; D002109:Caffeic Acids; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C040048:caffeic acid