Lack of flow regulation may explain the development of arteriovenous malformations

In the normal vasculature, vessels of widely different sizes maintain shear stress within a narrow range. Recently, investigators have had great success using mathematical models to explore the relationship of structure to function in normal vascular beds. When investigators first explored how vascular beds adapt to set shear stress at appropriate levels, however, some vessels tended to regress, and some tended to grow into arteriovenous shunts. Degeneration of the arterial tree is prevented when flow regulation is added to the model. The present work explores the implication of this theoretical development and illustrates how it may explain the genesis of arteriovenous malformations (AVMs). We use a simple model to illustrate how impairing local control of blood flow causes models to become structurally unstable, yielding a structure and behavior similar to AVMs. This work shows how the lack of local flow control can be the cause, not just the result, of arteriovenous malformations. With insight gained from this modeling approach, specific, focused experiments can be designed.