Stimulation des Aktin-Metabolismus ist ein Schlüsselmechanismus des Kollateralwachstums nach Gefäßverschluss - Bedeutung einer permanenten Erhöhung der longitudinalen Schubspannung

Prospective in vivo experiments to test the morphogenic power of increased fluid shear stress on collateral vessel growth (arteriogenesis) are rare. Therefore, the present study was designed to determine the arteriogenic potency of increased fluid shear stress and elucidate the underlying mechanism. Methods: Domestic pigs (n = 20) underwent bilateral proximal ligature of both superficial femoral arteries. At 1 week, a side-to-side anastomosis was created unilaterally between the distal femoral stump and the accompanying vein. Another week later, pressure and flow measurements in presence and absence of reactive hyperemia were performed to determine the fractional collateral flow (FCF). Quantitative arterial angiography was utilized for morphometric analysis of the collateral vessels. Subsequently, the vessels were excised and confocal immunohistochemistry (PCNA, eNOS, a-actin, lectin), as well as 2D-PAGE, differential expression analysis and Northern-blotting for destrin, cofilin-1, cofilin-2 and transgelin-2 was performed. Results: The number and size of collateral vessels was significantly increased in the shunted (S) as compared to the non-shunted (C) limb (p < 0,001; t-test). The mean fractional collateral flow was also significantly elevated (p<0,01). Immunohistochemistry confirmed a large number of PCNA-positive smooth muscle cells and endothelial cells and increased expression of lectin. eNOS expression was increased in collaterals, irrespective av-shunting. Cofilin-1, cofilin2, transgelin-2 and destrin displayed the highest degree of differential regulation in (S). Conclusions: Elevated shear stress is probably the most important physical molding force of arteriogenesis. Restart of the cell cycle of endothelial and smooth muscle cells and cytoskeletal re-arrangement of actin filaments are the key mechanisms that catalyze increased mobility during outward remodeling.