The role of hyaluronic acid in atherosclerosis and intimal hyperplasia

Abstract

Atherosclerosis is a chronic inflammatory condition of the blood vessel wall that can lead to arterial narrowing and subsequent vascular compromise. Although there are a variety of open and endovascular procedures used to alleviate the obstructions caused by atherosclerotic plaque, blood vessel instrumentation itself can lead to renarrowing of the vessel lumen through intimal hyperplasia, wound contracture, or a combination of the two. While the cell types involved in both atherosclerosis and vessel renarrowing after surgical intervention are largely characterized, current research has shown that components of the extracellular matrix are also important in the pathogenesis of the aforementioned processes. One such component is hyaluronic acid (HA). The objective of this review, therefore, is to examine the involvement of HA in these pathologic processes. Literature on the structure and function of HA was reviewed, with particular attention given to the role of HA in the processes of atherogenesis, intimal hyperplasia, and wound contracture after blood vessel instrumentation. HA interacts with vascular smooth muscle cells (VSMCs), endothelial cells (ECs), and platelets to promote atherogenesis. In particular, VSMCs manufacture large amounts of HA that form "cable-like" structures important for leukocyte adhesion and rolling. Additionally, transmigration of leukocytes across the EC layer is mediated by HA. Platelets cleave large molecules of HA into fragments that up-regulate leukocyte production of chemokines and cytokines. HA also has a role in both intimal hyperplasia and wound contracture, the two processes most responsible for vessel renarrowing after vascular instrumentation. HA has a complex, and sometimes conflicting, role in the pathologic processes of atherogenesis and vessel wall renarrowing after surgical intervention.