Altered flow-induced arterial remodeling in vimentin-deficient mice

The endothelial cytoskeleton plays a key role in arterial responses to acut e changes in shear stress. We evaluated whether the intermediate filament p rotein vimentin is involved in the structural responses of arteries to chro nic changes in blood flow (BF). In wild-type mice (V+/+) and in vimentin-de ficient mice (V-/-), the left common carotid artery (LCA) was ligated near its bifurcation, and 4 weeks later, the structures of the occluded and of t he contralateral arteries were evaluated and compared with the structures o f arteries from sham-operated mice. Body weight and mean carotid artery BF did not differ between the strains, but LCA and right carotid artery (RCA) diameter (737 +/- 14 mu m [LCA] and 723 +/- 14 mu m [RCA] for V-/- versus 8 08 +/- 20 mu m [LCA] and 796 +/- 20 E-Lm [RCA] for V+/+) and medial cross-s ectional area (CSAm) were significantly smaller in V-/- (21 +/- 1 and 22 +/ - 2 X 10(3) mu m(2) for LCA and RCA, respectively) than in V+/+ (28 +/- 2 a nd 28 +/- 3 X 10(3) mu m(2) for LCA and RCA, respectively). In V+/+, LCA li gation eliminated BF in the occluded vessel (before ligation, 0.35 +/- 0.02 mL/min) and increased BF from 0.34 +/- 0.02 to 0.68 +/- 0.04 mL/min in the RCA. In V-/-, the BF change in the occluded LCA was comparable (from 0.38 +/- 0.05 mL/min to zero-flow rates), but the BF increase in the RCA was les s pronounced (from 0.33 +/- 0.02 to 0.50 +/- 0.05 mL/min). In the occluded LCA of V+/+, arterial diameter was markedly reduced (-162 mu m), and CSAm w as significantly increased (5 X 10(3) mu m(2)), whereas in the high-flow RC A of V+/+, carotid artery diameter and CSAm were not significantly modified . In the occluded LCA of V-/-, arterial diameter was reduced to a lesser ex tent (-77 mu m) and CSAm was increased to a larger extent (10 X 10(3) mu m( 2)) than in V+/+. In contrast to V+/+, the high-flow RCA of V-/- displayed a significant increase in diameter (52 mu m) and a significant increase in CSAm (5 X 10(3) mu m(2)). These observations provide the first direct evide nce for a role of the cytoskeleton in flow-induced arterial remodeling, Fur thermore, they dissociate (1) between acute and chronic arterial responses to altered BF, (2) between alterations of lumen diameter and wall mass duri ng arterial remodeling, and (3) between developmental and imposed flow-indu ced arterial remodeling.