Moderately elevated plasma homocysteine impairs functional endothelial recovery following denudation of mouse carotid arteries.
Increased total plasma homocysteine is an independent risk factor for cardiovascular disease. This study was designed to determine whether it can impair endothelial function, by examining the recovery of acetylcholine-evoked relaxation following mechanical denudation of the endothelium in the arteries of cystathionine beta-synthase knockout (CbetaS(+/-)) mice. Heterozygous CbetaS(+/-) mice had total plasma homocysteine concentrations significantly higher (8.9 +/- 1.1 micromol/L, n = 12) than strain-matched wild-types (4.6 +/- 0.4 micromol/L, n = 5; P =.003). Left common carotid arteries were denuded of endothelium using a 250-microm polytetrafluoroethylene filament. After 10 days, when the endothelium had completely regrown, relaxation to acetylcholine was measured in precontracted segments of artery. Uninjured right carotid arteries from the same animals served as internal controls. Relaxation to acetylcholine was significantly attenuated in the injured arteries of the CbetaS(+/-) mice, compared to wild-types (P =.017); furthermore, there was a significant negative correlation between sensitivity to acetylcholine and total plasma homocysteine concentration measured in the same animal (r = -0.69, P <.003). These data suggest that even modest homocysteinemia has a deleterious effect on the function of healed endothelium in mouse arteries. This may account for its adverse influence on chronic cardiovascular disease.
Miller
Alastair L
AL
Bristol Heart Institute, University of Bristol, Bristol, UK.
Witchel
Harry J
HJ
Hancox
Jules C
JC
Jackson
Christopher L
CL
Jeremy
Jamie Y
JY
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology; D017536:Carotid Artery, Common / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D003541:Cystathionine beta-Synthase / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006710:Homocysteine / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D020127:Recovery of Function; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D006710:Homocysteine; D003541:Cystathionine beta-Synthase; D000109:Acetylcholine