Abstract
Fluid shear stress (FSS) is the pivotal trigger of peripheral arteriogenesis. The aim of this study was to investigate the impact of fluid shear stress on cerebral arteriogenesis as well as to compare expression profiles and feasibilities of drug modulation to peripheral arteriogenesis. In this study three new models to increase FSS in cerebral collaterals were established. Blood flow changes ...
Abstract
Fluid shear stress (FSS) is the pivotal trigger of peripheral arteriogenesis. The aim of this study was to investigate the impact of fluid shear stress on cerebral arteriogenesis as well as to compare expression profiles and feasibilities of drug modulation to peripheral arteriogenesis. In this study three new models to increase FSS in cerebral collaterals were established. Blood flow changes were monitored by quantitative magnetic resonance imaging (MRI) analysis and cerebral arteriogenesis was analyzed by MRI and contrast agent angiography. The expression of messenger RNA (mRNA) was determined by quantitative real-time PCR (qRT-PCR) and of protein expression by immunohistochemistry. Drugs were applied via osmotic minipumps. During the 14-day observation period, comparative analysis indicated a correlation between the growth of cerebral collaterals and increasing intravascular flow rates. Expression profiling showed similarities concerning endothelial cell-expressed genes but differences concerning genes expressed in smooth muscle cells. Highest expression was found for the FSS-sensitive, endothelial cell-expressed transient receptor potential cation channel subfamily V member 4 (Trpv4). Application of a Trpv4 activator significantly enhanced cerebral arteriogenesis. Fluid shear stress is also the pivotal trigger of cerebral arteriogenesis. Signal transduction of cerebral arteriogenesis differs from peripheral arteriogenesis. Trpv4 seems to be an interesting candidate for the development of new therapeutic concepts.
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