Red wine prevents homocysteine-induced endothelial dysfunction in porcine coronary arteries

J Surg Res. 2003 Nov;115(1):82-91. doi: 10.1016/s0022-4804(03)00247-6.


Background: Hyperhomocysteinemia is an independent risk factor of coronary artery disease. Clinical studies have indicated that moderate red wine consumption is associated with a reduction of incidence of coronary artery disease. In this study, we determined the effect of red wine on homocysteine- induced endothelial dysfunction in porcine coronary arteries.

Materials and methods: Porcine coronary arteries were dissected from 6 pig hearts and cut into 5-mm ring segments, which were assigned into 4 groups (9 rings/group): blank control, homocysteine treated (50 muM), red wine treated (0.08% alcohol), and homocysteine plus red wine treated. The rings were cultured in cell culture medium with or without treatment for 24 h. Myograph analysis was performed with U46619 (10(-7) M) for contraction and cumulative bradykinin (10(-9) to 10(-5) M) for endothelium-dependent relaxation. The endothelial nitric oxide synthase (eNOS) levels were analyzed by RT-PCR, Western blot, and immunohistochemistry.

Results: In response to 10(-5) M bradykinin, porcine coronary artery rings treated with homocysteine (50 muM) showed a significant reduction of endothelium-dependent vasorelaxation by 43% as compared to controls (P < 0.05). However, rings treated with red wine (0.08% alcohol) plus homocysteine showed no significant difference as compared to controls. Endothelium-dependent vasorelaxation was not different between control and red wine treated groups. Furthermore, eNOS mRNA density levels were significantly reduced by 36% in homocysteine treated group as compared to controls (P < 0.05). eNOS protein levels were also substantially reduced in the homocysteine-treated group. However, red wine treatment reversed the effect of homocysteine-induced eNOS downregulation.

Conclusions: Homocysteine significantly impaired endothelial functions including endothelium-dependent vasorelaxation and eNOS mRNA and protein levels in porcine coronary arteries; and red wine effectively prevented homocysteine-induced endothelial dysfunction. This study suggests that protecting coronary endothelial cells from homocysteine damage may be an important mechanism of red wine for preventing coronary artery disease.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
  • Animals
  • Blotting, Western
  • Bradykinin / administration & dosage
  • Coronary Disease / etiology
  • Coronary Disease / prevention & control
  • Coronary Vessels / drug effects*
  • Coronary Vessels / enzymology
  • Coronary Vessels / physiology
  • Culture Media
  • Culture Techniques
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / physiology
  • Gene Expression / drug effects
  • Homocysteine / pharmacology*
  • Immunohistochemistry
  • Muscle Contraction / drug effects
  • Muscle Relaxation / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Synthase / analysis
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase Type III
  • Nitroprusside / pharmacology
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Swine
  • Wine*


  • Culture Media
  • Nitric Oxide Donors
  • RNA, Messenger
  • Homocysteine
  • Nitroprusside
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Bradykinin