title: Folate supplementation inhibits intimal hyperplasia induced by a high-homocysteine diet in a rat carotid endarterectomy model.
abstract: OBJECTIVE
  Hyperhomocysteinemia has been implicated as a causative factor in intimal hyperplasia development. The addition of dietary folate in a hyperhomocysteinemia, carotid endarterectomy rat model is postulated to decrease plasma homocysteine levels and, in turn, reduce post-carotid endarterectomy intimal hyperplasia.
  
  
  METHODS
  Each rat was fed one of six diets: (1) lab chow with no folate (n = 7), (2) lab chow with 10 mg/kg folate added (n = 3), (3) lab chow with 25 mg/kg folate added (n = 3), (4) a homocysteine diet with no folate (n = 7), (5) a homocysteine diet with 10 mg/kg folate added (n = 5), or (6) homocysteine diet with 25 mg/kg folate added (n = 5). Each rat then underwent an open carotid endarterectomy. In 2 weeks, intimal hyperplasia in the carotid artery was measured. Plasma homocysteine and folate levels were measured.
  
  
  RESULTS
  Plasma folate levels rose with folate administration. Plasma homocysteine in the lab chow group was 5.4 +/- 0.5 micromol/L and did not change with the addition of folate. In the homocysteine diet group, plasma homocysteine rose 10-fold over the lab chow group (51.9 +/- 6.5 vs 5.4 +/- 0.5, micromol/L, P <.0001). In the group fed a homocysteine diet with 10 mg/kg folate added, a significant decrease in plasma homocysteine was observed (17.5 +/- 8.5 vs 51.9 +/- 6.5, micromol/L, P =.0003). In the group fed a homocysteine diet with 25 mg/kg folate added, plasma homocysteine levels were further reduced to levels seen in the lab chow group (12.6 +/- 2.6 vs 5.4 +/- 0.5, micromol/L, P = not significant). The relationship between plasma folate and homocysteine was inverse (R = 0.39, P =.0036). Luminal stenosis due to intimal hyperplasia was minimal in lab chow groups and unaffected by folate. The homocysteine diet group demonstrated post-carotid endarterectomy luminal stenosis due to intimal hyperplasia (60.9% +/- 9.2%). In the group fed a homocysteine diet with 10 mg/kg folate added, intimal hyperplasia was reduced, compared with the homocysteine diet group (32.6% +/- 7.4% vs 60.9% +/- 9.2%, P =.009). In the group fed a homocysteine diet with 25 mg/kg folate added, intimal hyperplasia was reduced to lab chow group levels (10.8% +/- 0.8% vs 4.8% +/- 1.0%, P = not significant) and was reduced, compared with the group fed a homocysteine diet with 10 mg/kg folate added.
  
  
  CONCLUSIONS
  The use of folate in this hyperhomocysteinemia carotid endarterectomy model and the resultant attenuation of plasma homocysteine elevation and intimal hyperplasia development lend strong support to homocysteine being an independent etiologic factor in post-carotid endarterectomy intimal hyperplasia.
authors.affiliation: Department of Surgery, Division of Vascular Surgery, Central Arkansas Veterans Health Care System, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: Smith
authors.forename: C P
authors.initials: CP
authors.lastname: Cruz
authors.forename: A T
authors.initials: AT
authors.lastname: Brown
authors.forename: J F
authors.initials: JF
authors.lastname: Eidt
authors.forename: M M
authors.initials: MM
authors.lastname: Moursi
mesh_terms: D000818:Animals; D019587:Dietary Supplements; D004195:Disease Models, Animal; D016894:Endarterectomy, Carotid; D005492:Folic Acid / Q000494:pharmacology*; D006710:Homocysteine / Q000008:administration & dosage*; D006965:Hyperplasia / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology*
chemical_list: D006710:Homocysteine; D005492:Folic Acid