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The cardio

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									The Cardiovascular Protective
     Effect of Red Wine

         Bao-Ping Chen
            Background


 The association between alcohol
consumption and the low incidence of
coronary artery disease (CAD)
 The inverse relationship between red
wine consumption and mortality from
ischemic heart disease
 French Paradox
 Arteriosclerosis
 Components of red wine
 Inhibition of LDL oxidation
 Inhibition of vascular smooth muscle
cell proliferation and migration
 Modulation of platelet aggregation
 Effects on vasomotor tone
 Effects on HDL
               Arteriosclerosis


 Definition
Arteriosclerosis is a multifactorial disease
process and is the principal cause of myocardial
infarction, stroke, and peripheral vascular disease,
accounting for almost 40% of all mortality in the
united states.
 Characteristics
(1) Plaque formation
(2) Progressive narrowing of the arterial’s lumen
diameter
            Formation of Arteriosclerosis
             Accumulation of lipids (fatty streak)

          Surrounded by prolifereating smooth muscle

              LDL enters the endothelium

          LDL becomes oxidized by several types of cells

   The oxidized LDL attracts macrophages, forming foam cells

     Proliferating smooth muscle, lipids, and connective tissue
     become incorporated into the maturing Plaque

Formation of a fibrous cap, having areas of cell necrosis and calcifation

             Narrowing of the arterial’s lumen diameter
     Red wine’s component


 Ethanol
 Polyphenolic
                          Ethanol
The effect of alcohol on the cardiovascular system
 Act as a fuel source
 Alter cholesterol composition
 Impair fluid balance
 Alter the activity of xenobiotic-metabolizing enzymes (p-450
cytochrome family, glutathione S-transferase superfamily, N-acetyl-
transferases, etc)
 Moderate consumption increase plasma concentrations of HDL
 Moderate consumption decrease the adhesiveness of platelets
 Increase polyphenol availability by improving intestinal absorption
 Has a prooxidant effect (but polyphenols in alcoholic beverages
counteract the potential prooxidant effect of ethanol)
                   Ethanol

Comparison of red wine with spirits, beer and
white wine
 Beverages such as white wine and beer, which
have low levels of phenolic compounds, may have
a prooxidant effects; red wine has net antioxidant
activity
 In comparison to other alcoholic beverages
such as spirits, beer, and white wine, red wine is
the most beneficial in reducing the risks of CAD
and mortality in general
 Consumption of spirits was associated with an
increased risk in deaths from all causes and in
deaths from vascular diseases
1
      Polyphenol inhibition of LDL oxidation

LDL oxidation is a key event in atherogenesis

 Polyphenols reduce LDL sensitivity to peroxidation
 The susceptibility of LDL to copper-mediated oxidative modifications
was not influenced by the dealcoholized red wine
 The consumption of white wine actually has a prooxidant effect
 The effect could be explained by the prooxidative properties of alcohol
 Increasing the capacity of white wine to scavenge free radicals and to
inhibit LDL’s copper ion-induced oxidation when the fruit huices were
macerated with grape solida in the presence of increasing levels of
alcohol
 This led to the conclusion that red wine, but not white wine, has
important antioxidant activity because of the high content of polyphenols
Several potential mechanisms by which LDL is
protected from oxidation by phenolics

  As a free radical scavenger of hydrogen atom-
 donating molecules
  Through the chelation of transition metal ions by
 phenolics, diminishing the capacity of the metal to
 generate free radicals
  Sparing of vitamin E and carotenoids in the LDL
 particle
  Protecting or increasing serum paraoxonase activity
Polyphenol inhibition of vascular smooth
  muscle cell (SMC) proliferation and
               migration

 The abnormal proliferation of VSMC in the
arterial intima is a key step in the formation
the atherosclerotic plaque
 Red wine and red wine polyphenols inhibit
SMC proliferation in a dose-dependent
manner
Mechanisms of the antiproliferative effect
        of red wine on SMC

   Cell cycle arrest
      DNA strand breakage
      Decrease cycle A expression
   Inhibition of ICAM-1 AND VCM-1
   Inhibition of PDGF
      Inhibition of P13-K and P38mapk
   Inhibition of MMP 9
   Apoptosis
 Polyphenol modulation of platelet
          aggregation


 Decreased platelet aggregation is frequently
associated with low incidence and prevalence of
CAD
 Polyphenols have also been shown to inhibit
platelet aggregation, and this may account for
their cardioprotective properties
Mechanisms of polyphenol inhibiting
      platelet aggregation


 Inhibition of cyclo-oxygenase pathway
 Inhibition of thromboxane B-2 synthesis
 Potentiate prostaglandin I2
    Increase phosphodiesterases (cAMP.,
cGMP)
Polyphenol effects on vasomotor tone



 Red wine polyphenol’s beneficial
 property to induce NO release with the
 subsequent effect of vasorelaxation,
 resulting in a cardioprotective action
 Mechanisms of vasorelaxation by
          polyphenols


 eNOS expression
    NO release
 Resveratrol ----endothelial dependent
 Quercitin ----endothelial independent
     Polyphenol effects on HDL


Red wines are also capable of increasing
HDL. This lipid prevents cholesterol
accumulation in peripheral cells and is
protective against arteriosclerosis by
transporting cholesterol from the arteries to
the liver for its subsequent metabolism and
excretion.
 Mechanisms of increasing HDL by
          polyphenols



Increase apolipoproteins A-Ⅰ and A-Ⅱ

								
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