Cigarette smoke increases intimal hyperplasia and homocysteine in a rat carotid endarterectomy.
BACKGROUND
Homocysteine and smoking are independent risks for CVD; however their importance in post-CEA intimal hyperplasia is unclear. We performed a CEA in rats exposed to cigarette smoke with the hypothesis that smoking would increase intimal hyperplasia that may be associated with an elevated serum homocysteine. Folic acid (FA) and the homocysteine metabolic enzymes MTHFR and CBS were used to test for the significance of homocysteine elevation.


METHODS
Rats underwent an open CEA. N = 13 rats received smoke exposure 2 weeks prior, and 2 weeks post-CEA and N = 12 received no smoke. Each group was divided into either control or an FA-added diet resulting in four groups. Rats were sacrificed at 2 weeks post-CEA; liver, urine, blood, and carotid arteries samples were obtained.


RESULTS
Smoked rats had increased urinary peak and trough cotinine levels versus non-smoke rats, which decreased with FA. Smoke exposure increased intimal hyperplasia versus non-smoke controls by nearly 120% (57.8 +/- 6.2 versus 26.8 +/- 5.4% luminal stenosis, P = 0.005). Smoke-exposed rats had an increased serum homocysteine versus non-smoke controls (8.3 +/- 0.8 versus 5.7 +/- 0.8 microm, P = 0.014). Smoked rats given FA had decreased serum homocysteine compared to the smoke group. Along with reductions in homocysteine, FA eliminated the increase in intimal hyperplasia seen with smoke exposure (33.5 +/- 6.1 versus 57.8 +/- 6.2% luminal stenosis, P = 0.03). CBS activity decreased in smoked rats by nearly 20% versus non-smoke rats. FA supplementation in smoked rats both (1) increased CBS activity and (2) decreased MTHFR compared to control non-smoke-exposure levels.


CONCLUSIONS
Smoking increases plasma homocysteine and post-CEA intimal hyperplasia. This suggests homocysteine has an etiological role in the intimal hyperplasia increase observed with smoking, since both were negated with FA.
University of Arkansas for Medical Sciences, Central Arkansas Veterans HealthCare System, 4300 West 7th Street, Little Rock, AR 72205, USA.
Joseph A
JA
Davis
Aliza T
AT
Brown
Hongjiang
H
Chen
Yunfang
Y
Wang
Lionel A
LA
Poirier
John F
JF
Eidt
Carlos P
CP
Cruz
Mohammed M
MM
Moursi
D000818:Animals; D003367:Cotinine / Q000652:urine; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D016894:Endarterectomy, Carotid; D006710:Homocysteine / Q000097:blood*; D006965:Hyperplasia; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana; D017539:Tunica Intima / Q000473:pathology*
D012906:Smoke; D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003541:Cystathionine beta-Synthase; D003367:Cotinine