This Article Full Text Full Text (PDF) All Versions of this Article: 91/10/931    most recent 01.RES.0000041408.64867.1Dv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Baumbach, G. L. Articles by Lentz, S. R. Search for Related Content PubMed PubMed Citation Articles by Baumbach, G. L. Articles by Lentz, S. R. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB (L)-METHIONINE Related Collections Remodeling Cerebrovascular disease/stroke Animal models of human disease Hypertrophy Smooth muscle proliferation and differentiation

(Circulation Research. 2002;91:931.)
© 2002 American Heart Association, Inc.

Integrative Physiology

Structure of Cerebral Arterioles in Cystathionine ß-Synthase-Deficient Mice

Gary L. Baumbach, Curt D. Sigmund, Teodoro Bottiglieri, Steven R. Lentz

From the Departments of Pathology (G.L.B.) and Internal Medicine (C.D.S., S.R.L.), University of Iowa College of Medicine and Cardiovascular Center, Iowa City, Iowa; the Baylor Institute of Metabolic Disease (T.B.), Dallas, Tex; and the VA Medical Center (S.R.L.), Iowa City, Iowa.

Correspondence to Gary L. Baumbach, MD, Dept of Pathology, 105 Medical Laboratories, University of Iowa College of Medicine, Iowa City, IA 52242. E-mail g-baumbach{at}uiowa.edu

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 ß-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.

Key Words: hyperhomocysteinemia • cerebral arteriole • vascular hypertrophy

This article has been cited by other articles:

				S. Dayal and S. R. Lentz Murine Models of Hyperhomocysteinemia and Their Vascular Phenotypes Arterioscler Thromb Vasc Biol, September 1, 2008; 28(9): 1596 - 1605. [Abstract] [Full Text] [PDF]

				A. M. Troen, M. Shea-Budgell, B. Shukitt-Hale, D. E. Smith, J. Selhub, and I. H. Rosenberg B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice PNAS, August 26, 2008; 105(34): 12474 - 12479. [Abstract] [Full Text] [PDF]

				A. M. Beyer, G. L. Baumbach, C. M. Halabi, M. L. Modrick, C. M. Lynch, T. D. Gerhold, S. M. Ghoneim, W. J. de Lange, H. L. Keen, Y.-S. Tsai, et al. Interference With PPAR{gamma} Signaling Causes Cerebral Vascular Dysfunction, Hypertrophy, and Remodeling Hypertension, April 1, 2008; 51(4): 867 - 871. [Abstract] [Full Text] [PDF]

				G. L. Baumbach, S. P. Didion, and F. M. Faraci Hypertrophy of Cerebral Arterioles in Mice Deficient in Expression of the Gene for CuZn Superoxide Dismutase Stroke, July 1, 2006; 37(7): 1850 - 1855. [Abstract] [Full Text] [PDF]

				I. C. Duncan and J. M. Terblanche Spontaneous Isolated Posterior Communicating Artery Dissection in a Young Adult with Hyperhomocysteinemia AJNR Am. J. Neuroradiol., September 1, 2005; 26(8): 2030 - 2032. [Abstract] [Full Text] [PDF]

				G. Yang, K. Cao, L. Wu, and R. Wang Cystathionine {gamma}-Lyase Overexpression Inhibits Cell Proliferation via a H2S-dependent Modulation of ERK1/2 Phosphorylation and p21Cip/WAK-1 J. Biol. Chem., November 19, 2004; 279(47): 49199 - 49205. [Abstract] [Full Text] [PDF]

				G. L. Baumbach, C. D. Sigmund, and F. M. Faraci Structure of Cerebral Arterioles in Mice Deficient in Expression of the Gene for Endothelial Nitric Oxide Synthase Circ. Res., October 15, 2004; 95(8): 822 - 829. [Abstract] [Full Text] [PDF]

				S. Dayal, E. Arning, T. Bottiglieri, R. H. Boger, C. D. Sigmund, F. M. Faraci, and S. R. Lentz Cerebral Vascular Dysfunction Mediated by Superoxide in Hyperhomocysteinemic Mice Stroke, August 1, 2004; 35(8): 1957 - 1962. [Abstract] [Full Text] [PDF]

				A. M. Devlin, E. Arning, T. Bottiglieri, F. M. Faraci, R. Rozen, and S. R. Lentz Effect of Mthfr genotype on diet-induced hyperhomocysteinemia and vascular function in mice Blood, April 1, 2004; 103(7): 2624 - 2629. [Abstract] [Full Text] [PDF]

				F. M. Faraci and S. R. Lentz Hyperhomocysteinemia, Oxidative Stress, and Cerebral Vascular Dysfunction Stroke, February 1, 2004; 35(2): 345 - 347. [Full Text] [PDF]

				F. M. Faraci Hyperhomocysteinemia: A Million Ways to Lose Control Arterioscler Thromb Vasc Biol, March 1, 2003; 23(3): 371 - 373. [Full Text] [PDF]