Can Intimal Hyperplasia and Distal Anastomotic Intimal Hyperplasia be Controlled and Prevented?

Abstract

Intimal hyperplasia (IH) and distal anastomotic intimal hyperplasia (DAIH) are ubiquitous pathologic entities encountered in vessel wall and late graft occlusion following angioplasty, stenting, endarterectomy, or bypass procedures. Flow dynamice related wall shear stress, cytokines, and growth factors are known to mediate subendothelial myoblast proliferation and matrix production, the precursor of IH development. The configuration of distal anastomosis (size mismatched end-to-end or unphysiologic end-to-side) creates oscillatory or vortex turbulent flow patterns conducive to lowand high-shear stresses as well as endothelial process lifting, particularly at the toe more than the heel of end-to-side distal anastomosis. 1 Endothelial cell damage enhances thrombocytes, leukocytes, monocytes, and blood-borne elements entering the subendothelium to promote and mediate myoblast activities leading to DAIH production. 2-3 The role of growth factors and cytokine in DAIH pathogenesis is not well defined. Transmission electron microscopic DAIH analysis of occluded/stenosed human or canine arteries revealed cell transformation and cell orientation reflective of the dynamic process in IH and DAIH pathogenesis. 4-5 IH and DAIH is composed of well-organized multi-interlamination of myoblasts and fibrocollagen matrix of 80-130 lamellar units. 6 Concurrent cell transformation (from random distribution to well-organized multi-interlamination of cell and matrix) plus cell differentiation (from mesenchyme to myofibroblasts between the graft and the lumen) coupled with the specificity of DAIH distribution (heel, toe, and floor of end-to-side distal anastomosis), and the sequence of its development have also been documented. 7-9 Active research in the past few decades has compiled a large volume of data regarding the role of cytokines and growth factor in regulating endothelial gene expression. These substances have been linked to mediating subendothelial myoblast proliferation and matrix production. The latter are ingredients needed for IH and DAIH pathogenesis. In other words, without the participation of the synthetic capacity of myoblasts and myofibroblast, IH and DAIH will not occur despite the mediation by scores of cytokines and growth factors.