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(American Journal of Pathology. 2004;164:81-89.)
© 2004 American Society for Investigative Pathology

Early Adaptive Responses of the Vascular Wall during Venous Arterialization in Mice

Stephanie Kwei^*, George Stavrakis, Masaya Takahas, George Taylor^¶, M. Judah Folkman^*¶, Michael A. Gimbrone, Jr^¶ and Guillermo García-Cardeña^¶

From the Surgical Research Laboratories,^* Children’s Hospital, Boston; the Department of Pathology, Brigham and Women’s Hospital, Boston; the Department of Radiology, Beth Israel Deaconess Medical Center, Boston; the Department of Radiology, Children’s Hospital, Boston; and Harvard Medical School,^¶ Boston, Massachusetts

Venous arterialization occurs when a vein segment is transposed as a bypass graft into the arterial circulation, resulting in a structural and functional reorganization of the vascular wall in response to the new local biomechanical environment. Although the anatomical changes of venous arterialization have been well characterized, the molecular mechanisms of vascular remodeling remain incompletely understood. Here, we present a novel model of venous arterialization in mice wherein the external jugular vein is connected to the common carotid artery. The hemodynamic characteristics of the arterialized vein, as assessed by ultrasound and magnetic resonance imaging, resemble features of the arterial circulation. Temporal analyses of the morphological changes in the venous segment at 1, 3, and 7 days after surgery demonstrate preservation of the endothelium at all time points and formation of multiple smooth muscle layers by day 7. Expression of endothelial E-selectin and VCAM-1 was documented at early time points, concomitant with the presence of neutrophils and monocytes/macrophages in the vascular wall. In addition, endothelium-dependent permeability was decreased in the arterialized vein when compared to the contralateral control vein. Thus, this novel mouse model of venous arterialization displays anatomical and cellular features present in other species, and should help to characterize the molecular mechanisms of this adaptive response of the vascular wall to changes in its biomechanical environment.

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