Effects of Shear Forces and Pressure on Blood Vessel Function and Metabolism in a Perfusion Bioreactor.

Bovine saphenous veins (BSV) were incubated in a perfusion bioreactor to study vessel wall metabolism and wall structure under tissue engineering conditions. Group 1 vessels were perfused for 4 or 8 days. The viscosity of the medium was increased to that of blood in group 2. Group 3 vessels were additionally strained with luminal pressure. Groups 1-d through 3-d were similar except that BSV were endothelium-denuded before perfusion. Groups 1-a through 3-a used native vessels at elevated flow rates. Group 3 vessels responded significantly better to noradrenaline on day 4, whereas denuded vessels showed attenuated responses (p < 0.001). Tetrazolium dye reduction did not depend on perfusion conditions or time except for denuded vessels. pO(2) gradients across the vessels were independent of time and significantly higher in group 2 (p < 0.001). BSV converted glucose stoichiometrically to lactate except vessels of groups 3, 1-d, and 3-d which released more lactate than glucose could supply (p < 0.001). Group 1 vessels as well as all vessels perfused with elevated flow rates showed a loss of endothelial cells after 4 days, whereas group 2 and 3 vessels retained most of the endothelium. These data suggest that vessel metabolism was not limited by oxygen supply. Shear forces did not affect glucose metabolism but increased oxygen consumption and endothelial cell survival. Luminal pressure caused the utilization of energy sources other than glucose, as long as the endothelium was intact. Therefore, vessel metabolism needs to be monitored during tissue engineering procedures which challenge the constructs with mechanical stimuli

Genetics of Moyamoya disease

Moyamoya disease (MMD) is a disease pattern consisting of bilateral stenosis of the intracranial internal carotid arteries (ICA) accompanied by a network of abnormal collateral vessels that bypass the stenosis. Once symptomatic, insufficient cerebral blood flow or rupture of the fragile collaterals may cause stroke or hemorrhage, resulting in severe neurological dysfunction or death. The etiology of MMD is still unknown, although few associations with other diseases and environmental factors have been described. Strong regional differences in epidemiological data, as well as known familial cases, turned the focus to genetics for the insight into the disease's pathogenesis. Thus far, several reports have suggested specific genetic loci and individual genes as predisposing to MMD, but none have demonstrated reproducible results in independent cohorts. Small sample sizes, as well as a likely multifactorial origin, seem to be the most challenging tasks in identifying the disease-causing mechanisms. Once identified, susceptibility genes may allow preventive screening and a possible development of novel therapeutic options