6 - Molecular approaches to revascularisation in peripheral vascular disease

Summary

INTRODUCTION

Currently, treatment options for peripheral vascular disease include angioplasty and reconstructive surgery. An attractive, less invasive alternative could involve the revascularization of ischaemic tissue by the induction of vascular growth. It would be particularly welcome for patients in whom current approaches are difficult or prone to failure, including those with conditions that make surgical intervention unsafe, patients with diffuse occlusive disease and those in whom there is significant downstream microvascular disease. Recent years have witnessed major advances in the understanding of the molecular mechanisms underlying vascular formation and remodelling, as well as the identification of key molecules controlling these processes. Most research has focused on the induction of new vessel formation by stimulating angiogenesis and this has been the goal of the clinical trials directed at peripheral vascular disease. But, whilst the stimulation of angiogenesis may relieve microvascular disease, the bypass of occluded conduit vessels requires the formation of more substantial collateral vessels by the process of arteriogenesis. This chapter will review current understanding of the mechanisms controlling angiogenesis and arteriogenesis; approaches that are, and could be pursued to induce vessel growth in peripheral vascular disease, as well as summarizing the current status of clinical trials.

MECHANISMS OF VASCULAR GROWTH

Strategies currently being developed for the therapeutic induction of vessel growth have evolved, largely, from knowledge of the physiological mechanisms of developmental vascularisation. In development, blood vessels arise initially by the process of vasculogenesis during which precursor cells, known as angioblasts, differentiate into endothelial cells and organize into primitive vessels.