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Structure of cerebral arterioles in cystathionine beta-synthase-deficient mice
Gary L Baumbach1, Curt D Sigmund, Teodoro Bottiglieri
1Department of Pathology, University of Iowa College of Medicine and Cardiovascular Center, Iowa City, Iowa 52242, USA. g-baumbach@uiowa.edu
Insights
Elevated homocysteine levels in mice caused cerebral arteriole thickening and increased vessel flexibility. This suggests hyperhomocysteinemia may contribute to stroke risk by altering brain blood vessel structure and mechanics.
Area of Science:
- Cardiovascular Science
- Neurology
- Biochemistry
Background:
- Hyperhomocysteinemia, elevated homocysteine levels, is a risk factor for cardiovascular and cerebrovascular diseases.
- The precise mechanisms by which hyperhomocysteinemia affects cerebral vasculature remain incompletely understood.
Purpose of the Study:
- To investigate the impact of hyperhomocysteinemia on the structure and mechanical properties of cerebral arterioles.
- To determine if elevated homocysteine levels induce changes in cerebral arteriole wall thickness and distensibility.
Main Methods:
- Utilized heterozygous cystathionine beta-synthase-deficient (CBS(+/-)) mice and wild-type (CBS(+/+)) littermates.
- Administered control and high-methionine diets to induce varying levels of plasma total homocysteine (tHcy).
- Measured plasma tHcy, and in vivo pressure, diameter, and cross-sectional area of maximally dilated cerebral arterioles.
Main Results:
- Hyperhomocysteinemia significantly increased plasma tHcy levels in both CBS(+/+) and CBS(+/-) mice, particularly with the high-methionine diet.
- Cerebral arteriole wall cross-sectional area was significantly increased in mice with hyperhomocysteinemia compared to controls.
- Stress-strain analysis revealed increased distensibility of cerebral arterioles in mice with elevated plasma tHcy.
Conclusions:
- Hyperhomocysteinemia is associated with cerebral vascular hypertrophy (thickening) in mice.
- Elevated homocysteine levels lead to increased distensibility and altered mechanical properties of cerebral arterioles.
- These vascular changes may contribute to the heightened stroke risk observed in individuals with hyperhomocysteinemia.
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 beta-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 micro mol/L in CBS(+/+) mice and 8.3+/-0.9 micro mol/L in CBS(+/-) mice (P<0.05 versus CBS(+/+) mice) fed the control diet. Plasma tHcy was 17.2+/-4.6 micro mol/L in CBS(+/+) mice and 21.2+/-3.9 micro mol/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 micro m(2)) mice fed control diet and CBS(+/+) (442+/-36 micro m(2)) and CBS(+/-) (471+/-46 micro m(2)) mice fed high-methionine diet relative to CBS(+/+) (324+/-18 micro m(2)) 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.