Asymmetric Cortical Vessel Sign Indicates Hemodynamic Deficits in Adult Patients with Moyamoya Disease.

BACKGOUND: Asymmetric cortical vessel sign (ACVS) on susceptibility-weighted imaging (SWI) indicates elevated concentration of deoxyhemoglobin and elevated oxygen extraction fraction in patients with cerebral ischemia. This study aimed to clarify whether ACVS is associated with impaired hemodynamics and hyperperfusion syndrome in patients with moyamoya disease (MMD). METHODS: Consecutive adult patients with MMD were enrolled. ACVS data on SWI and perfusion data using dynamic perfusion computed tomography were obtained and evaluated preoperatively and on postoperative days 2 and 180. RESULTS: A total of 24 patients with MMD were enrolled. Of 11 (45.83%) patients showing positive ACVS before surgery, 8 turned negative on postoperative day 2 and 9 showed absence of ACVS 180 days after surgery. Regions of interest showing positive ACVS had lower cerebral blood flow (CBF, P<0.001), increased cerebral blood volume (P = 0.021), prolonged time to peak (P<0.001), and mean transit time (P = 0.009). No patients with hemorrhagic symptoms showed positive ACVS(P = 0.041) and patients with positive ACVS showed more increase in CBF (P<0.004). CONCLUSIONS: In patients with MMD, ACVS on SWI indicates severe impairment in hemodynamics and is associated with more increase in CBF after bypass surgery. Hence, ACVS on SWI might be considered as a neuroimaging marker for the evaluation of hemodynamics in patients with MMD.

Homocysteine-mediated expression of SAHH, DNMTs, MBD2, and DNA hypomethylation potential pathogenic mechanism in VSMCs.

Homocysteine (Hcy) is a well-established risk factor for atherosclerosis and may cause dysregulation of gene expression, but the characteristics and the key links involved in its pathogenic mechanisms are still poorly understood. The aim of this study was to explore (i) the effects of Hcy on DNA methylation in vascular smooth muscle cells (VSMCs) and (ii) the underlying mechanism of Hcy-induced changes in DNA methylation patterns in relation to atherosclerosis. We examined the levels of gDNA methylation, namely, the Alu and line-1 element sequences, which can serve as a surrogate marker for gDNA methylation, and also investigated the effects of Hcy on the intracellular S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) concentrations as well as the expressions of SAH hydrolase (SAHH), DNA methyltransferase3a (DNMT3a), DNMT3b, and methyl-CpG-binding domain 2 (MBD2). We found that clinically relevant levels of Hcy (0-500 microM) induced elevation of SAH, declination of SAM and SAM/SAH ratio, and reduction in expression of SAHH and MBD2, but increased the activity of DNMT3a and DNMT3b compared to the control group (p < 0.05). We found also that the genome-wide hypomethylation is a common feature of gDNA in the VSMCs cultured with Hcy. In conclusion, these results suggest that Hcy-induced DNA methylation may be an important potential pathogenic mechanism in the development of atherosclerosis, and may become a therapeutic target for preventing Hcy-induced atherosclerosis.