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(Circulation Research. 2006;99:801.)
© 2006 American Heart Association, Inc.

Reviews

Allograft Vasculopathy Versus Atherosclerosis

Maziar Rahmani^*, Rani P. Cruz^*, David J. Granville, Bruce M. McManus

From The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Providence Research Institute; and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Correspondence to David J. Granville, PhD, or Bruce M. McManus, MD, PhD, FRSC, The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St. Paul’s Hospital, Rm 166-1081, Burrard St, Vancouver, BC, V6Z 1Y6, Canada. E-mail dgranville{at}mrl.ubc.ca or bmcmanus@mrl.ubc.ca

This Review is part of a thematic series on Transplant Vasculopathy, which includes the following articles:

Allograft Vasculopathy Versus Atherosclerosis

Stem Cells and Transplant Vasculopathy

Vascular Remodeling and Transplant Vasculopathy

Cytokines, Interferon-, and Transplant Vasculopathy

Chemokines and Transplant Vasculopathy

Antibody and Complement and Transplant Vasculopathy
William Baldwin and Jordan Pober Guest Editors

Over the last 4 decades, heart transplantation (HTx) has evolved as a mainstream therapy for heart failure. Approximately half of patients needing HTx have organ failure consequent to atherosclerosis. Despite advances in immunosuppressive drugs, long-term success of HTx is limited by the development of a particular type of coronary atherosclerosis, referred to as cardiac allograft vasculopathy (CAV). Although the exact pathogenesis of CAV remains to be established, there is strong evidence that CAV involves immunologic mechanisms operating in a milieu of nonimmunologic risk factors. The immunologic events constitute the principal initiating stimuli, resulting in endothelial injury and dysfunction, altered endothelial permeability, with consequent myointimal hyperplasia and extracellular matrix synthesis. Lipid accumulation in allograft arteries is prominent, with lipoprotein entrapment in the subendothelial tissue, through interactions with proteoglycans. The apparent endothelial "intactness" in human coronary arteries of the transplanted heart suggest that permeability and function of the endothelial barrier altered. Various insults to the vascular bed result in vascular smooth muscle cell (SMC) activation. Activated SMCs migrate from the media into the intima, proliferate, and elaborate cytokines and extracellular matrix proteins, resulting in luminal narrowing and impaired vascular function. Arteriosclerosis is a broad term that is used to encompass all diseases that lead to arterial hardening, including native atherosclerosis, postangioplasty restenosis, vein bypass graft occlusion, and CAV. These diseases exhibit many similarities; however, they are distinct from one another in numerous ways as well. The present review summarizes the current understanding of the risk factors and the pathophysiological similarities and differences between CAV and atherosclerosis.

Key Words: allograft vasculopathy • atherosclerosis • cardiac transplantation • chronic transplant rejection • risk factorspathogenesis • spathogenesis

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