Collateral blood vessels in stroke and ischemic disease: Formation, physiology, rarefaction, remodeling

Collateral blood vessels are unique, naturally occurring endogenous bypass vessels that provide alternative pathways for oxygen delivery in obstructive arterial conditions and diseases. Surprisingly however, the capacity of the collateral circulation to provide protection varies greatly among individuals, resulting in a significant fraction having poor collateral circulation in their tissues. We recently reviewed evidence that the presence of naturally-occurring polymorphisms in genes that determine the number and diameter of collaterals that form during development (ie, genetic background), is a major contributor to this variation. The purpose of this review is to summarize current understanding of the other determinants of collateral blood flow, drawing on both animal and human studies. These include the level of smooth muscle tone in collaterals, hemodynamic forces, how collaterals form during development (collaterogenesis), de novo formation of additional new collaterals during adulthood, loss of collaterals with aging and cardiovascular risk factor presence (rarefaction), and collateral remodeling (structural lumen enlargement). We also review emerging evidence that collaterals not only provide protection in ischemic conditions but may also serve a physiological function in healthy individuals. Primary focus is on studies conducted in brain, however relevant findings in other tissues are also reviewed, as are questions for future investigation.