title: Antithrombotic effect of grape seed proanthocyanidins extract in a rat model of deep vein thrombosis.
abstract: OBJECTIVE
  Proanthocyanidins are abundantly found in grape seeds and have been suggested to inhibit the pathogenesis of systemic diseases. We investigated the antithrombotic effects of proanthocyanidins in a rat model of deep vein thrombosis (DVT) and examined the underlying mechanisms.
  
  
  METHODS
  DVT was induced in rat model by inferior vena cava (IVC) ligation. Grape seed proanthocyanidins extract (GSPE, 400 mg/kg/d) dissolved in saline (2 mL) was orally administered to the experimental rats. Control rats were administrated saline (2 mL) only. The thrombi were harvested and weighed. The IVC was analyzed histologically and by transmission electron microscopy. The cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay. Expression of cellular adhesion molecules (CAMs) in thrombi was examined by Western blot.
  
  
  RESULTS
  GSPE significantly reduced thrombus length and weight (P < .01) and protected the integrity of the endothelium. GSPE inhibited thrombogenesis-promoting factors P-selectin, von Willebrand factor, and CAMs, and promoted thrombogenesis-demoting factors CD34, vascular endothelial growth factor receptor-2, and ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type one motif, member 13). Compared with the control, GSPE significantly lowered the cytokines IL-6 (74.19 ± 13.86 vs 189.54 ± 43.76 pg/mL; P < .01), IL-8 (80.71 ± 21.42 vs 164.56 ± 39.54 pg/mL; P < .01), and TNF-α (43.11 ± 17.58 vs 231.84 ± 84.11 pg/mL; P < .01).
  
  
  CONCLUSIONS
  GSPE significantly inhibited the propagation of thrombus induced by IVC ligation in a rat model. The antithrombotic properties of proanthocyanidins are likely to be directly associated with endothelial protection and regeneration, platelet aggregation, and inhibition of inflammatory cell and thrombus adhesion. Thus, proanthocyanidins may have a clinical application in DVT treatment.
authors.affiliation: First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yunjian
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hanping
authors.initials: H
authors.lastname: Shi
authors.forename: Wenjian
authors.initials: W
authors.lastname: Wang
authors.forename: Zunfu
authors.initials: Z
authors.lastname: Ke
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhong
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Li
authors.forename: Shenming
authors.initials: S
authors.lastname: Wang
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000071120:ADAMTS13 Protein; D000284:Administration, Oral; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015153:Blotting, Western; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008026:Ligation; D008297:Male; D046529:Microscopy, Electron, Transmission; D019007:P-Selectin / Q000378:metabolism; D044945:Proanthocyanidins / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012639:Seeds; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014682:Vena Cava, Inferior / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery / Q000648:ultrastructure; D020246:Venous Thrombosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D027843:Vitis / Q000737:chemistry; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D005343:Fibrinolytic Agents; D015850:Interleukin-6; D016209:Interleukin-8; D019007:P-Selectin; D044945:Proanthocyanidins; D014409:Tumor Necrosis Factor-alpha; D014841:von Willebrand Factor; D040301:Vascular Endothelial Growth Factor Receptor-2; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C512067:Adamts13 protein, rat