Structure of cerebral arterioles in cystathionine β-synthase-deficient mice

Abstract

We examined effects of hyperhomocysteinemia on structure and mechanics of cerebral arterioles. We measured plasma total homocysteine (tHcy) and pressure, diameter, and cross-sectional area of the vessel wall in maximally dilated cerebral arterioles in heterozygous cystathionine β-synthase-deficient (CBS+/-) mice and wild-type (CBS+/+) littermates that were provided with drinking water that was unsupplemented (control diet) or supplemented with 0.5% L-methionine (high-methionine diet). Plasma tHcy was 5.0±1.1 μmol/L in CBS-/+ mice and 8.3±0.9 μmol/L in CBS+/- mice (P<0.05 versus CBS-/+ mice) fed the control diet. Plasma tHcy was 17.2±4.6 μmol/L in CBS+/- mice and 21.2±3.9 μmol/L in CBS+/- mice (P<0.05) fed the high-methionine diet. Cross-sectional area of the vessel wall was significantly increased in CBS+/- (437±22 μm2) mice fed control diet and CBS+/+ (442±36 μm2) and CBS+/- (471±46 μm2) mice fed high-methionine diet relative to CBS+/+ (324±18 μm2) mice fed control diet (P<0.05). During maximal dilatation, the stress-strain curves in cerebral arterioles of CBS-/- mice on control diet and CBS-/+ and CBS+/- mice on high-methionine diet were shifted to the right of the curve in cerebral arterioles of CBS-/+ mice on control diet, an indication that distensibility of cerebral arterioles was increased in mice with elevated levels of plasma tHcy. Thus, hyperhomocysteinemia in mice was associated with hypertrophy and an increase in distensibility of cerebral arterioles. These findings suggest that hyperhomocysteinemia promotes cerebral vascular hypertrophy and altered cerebral vascular mechanics, both of which may contribute to the increased incidence of stroke associated with hyperhomocysteinemia.