Neointimal hyperplasia in balloon-injured rat carotid arteries: the influence of hyperhomocysteinemia.
OBJECTIVE
Hyperhomocyst(e)inemia (hH[e]) is a risk factor for atherosclerosis. Neointimal hyperplasia (NH) after vessel injury can contribute to atherosclerosis. In this study, we investigated the effects of hH(e) on NH formation after arterial balloon injury in rats.


METHODS
Lewis rats that were given a hH(e)-inducing (high methionine, low folate) or normal diet for 150 days underwent common carotid artery (CCA) balloon injury. Two and 4 weeks after injury, CCAs were formalin perfusion-fixed, sectioned, and stained for elastin. Neointimal index (NI, percent lumen occlusion) and neointima (N) and media (M) area were measured by using computer-interfaced microscopy.


RESULTS
Plasma homocyst(e)ine (H[e]) levels were elevated in rats given the study diet compared with rats given the normal diet at days 40 and 90 (69 +/- 8 and 73 +/- 9 micromol/L vs 4 +/- 0.4 and 4 +/- 0.6 micromol/L, P <.001). After balloon injury, the CCA NI and N/M ratio, but not the M area, were increased by hH(e) compared with normal plasma H(e) (2 weeks [n = 6,7]: NI = 7.3 +/- 1.7 vs 2.9 +/- 0.7, P =.002, and N/M = 0.31 +/- 0.08 vs 0.08 +/- 0.02, P <.001; 4 weeks [n = 4,7]: NI = 13.1 +/- 2.2 vs 6.3 +/- 1.3, P =.002, and N/M = 0.36 +/- 0.08 vs 0.17 +/- 0.03, P <.001).


CONCLUSIONS
hH(e) accelerates NH in a rat CCA balloon-injury model. The effect of hH(e) on NH may contribute to increased atherosclerosis in humans with hH(e).
Cook
Judith W
JW
Division of Liver/Pancreas Transplantation, Hepatobiliary Surgery, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd., Portland, OR 97201, USA.
Malinow
M Rene
MR
Moneta
Gregory L
GL
Taylor
Lloyd M
LM
Orloff
Susan L
SL
D000818:Animals; D020212:Carotid Artery Injuries / Q000150:complications / Q000209:etiology* / Q000473:pathology*; D017536:Carotid Artery, Common / Q000473:pathology*; D002404:Catheterization / Q000009:adverse effects*; D004195:Disease Models, Animal; D006710:Homocysteine / Q000097:blood; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications*; D006965:Hyperplasia / Q000150:complications / Q000209:etiology* / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D017539:Tunica Intima / Q000293:injuries* / Q000473:pathology*
D006710:Homocysteine