Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

Hemodynamic forces in the vasculature regulate normal arterial tone and structure as well as influence the pathophysiology of vascular anomalies. Wall shear stress, the tractive frictional force exerted by flowing blood upon the intimal endothelium, has been shown to elicit a wide range of physiologic (1,2), biochemical, and molecular (3,4,5,6) responses in both cell culture and whole animal experiments. Immediate shear stress-dependent dilation (7,8,9) as well as chronic luminal enlargement from elevated blood flow (10,11) have been well characterized. Results from these studies suggest that acute changes in vascular tone and long-term alterations in structural diameter are regulated by blood flow through endothelial-dependent mechanisms which act to restore wall shear forces towards normal homeostatic levels. Despite much investigation into vascular remodeling from changes in blood flow, the exact nature of the vessel wall alterations as well as the sequence of events involved in flow-mediated vessel auto-regulation remain unclear.

The mechanistic pathways involved in flow-mediated vascular remodeling have been investigated by numerous laboratories (4,12-16). Various transcription factors, growth factors, and cytokines have been suggested as candidates involved in flow-mediated signaling pathways under cell culture conditions. These include nuclear factor kappa B and AP-1 (4), basic FGF (12), TGF_ß1 (13), ET-1 (14), and PDGF (12,15,16). Despite these findings, little information is available regarding the role of growth factors in mediating vessel remodeling under in vivo conditions. Two possible mechanisms exist for the involvement of growth factors in the signal transduction pathway under physiologic conditions. First, elevated wall shear stress may induce the expression of endothelial shear stress-sensitive growth factors, followed by abluminal release to produce autocrine as well as paracrine responses. Second, shear stress-induced vasodilatation, via upregulation of NOS and subsequent NO production, elevates circumferential hoop stress which can stimulate the expression of growth factors specific to the medial layer. The overall aim of this study, therefore, was to characterize arterial remodeling and its sequence of events in rat mesenteric vessels exposed to blood flow alterations under in vivo physiologic conditions. Modification of an existing model (11) made it possible to evaluate in the same animal small arteries exposed to two different degrees of blood flow elevation over a 7 day period without alteration of the distending arterial pressure. Immunohistochemical and in situ hybridization procedures were employed in order to analyze the contribution of EC and SMC hyperplasia, eNOS, and PDGF-A in mediating flow-induced arterial remodeling.

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