doi: 10.1161/01.RES.0000261982.76892.09
© 2007 American Heart Association, Inc.
Reviews |
Vascular Remodeling in Transplant Vasculopathy
From the Department of Pathology (R.N.M.), Brigham and Women’s Hospital, Harvard Medical School; and The Donald W. Reynolds Cardiovascular Clinical Research Center (P.L.), Cardiovascular Division, Department of Medicine, Harvard Medical School, Boston, Mass.
Correspondence to Richard N. Mitchell, MD, PhD, Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, 77 Ave Louis Pasteur, Boston, MA 02115. E-mail rmitchell{at}rics.bwh.harvard.edu
This Review is part of a thematic series on Transplant Vasculopathy, which includes the following articles:
Allograft Vasculopathy Versus Atherosclerosis
Antibody and Complement in Transplant Vasculopathy
Interferon-
Axis in Graft Arteriosclerosis
Vascular Remodeling in Transplant Vasculopathy
Chemokines and Transplant Vasculopathy
Stem Cells and Transplant Vasculopathy
William M. Baldwin III and Jordan Pober Guest Editors
As therapeutic strategies to prevent acute rejection progressively improve, transplant vasculopathy (TV) constitutes the single most important limitation for long-term functioning of solid organ allografts. In TV, allograft arteries characteristically develop severe, diffuse intimal hyperplastic lesions that eventually compromise luminal flow and cause ischemic graft failure. Traditional immunosuppressive strategies that check acute allograft rejection do not prevent TV; indeed 50% of transplant recipients will have significant disease within five years of organ transplantation, and 90% will have significant TV a decade after their surgery. TV can involve the entire length of the transplanted arterial bed, including penetrating intraorgan arterioles. Indeed, the luminal narrowing of such penetrating vessels may be the most functionally significant because arterioles represent the major contributors to tissue vascular resistance. Because of the diffuseness of TV involvement in the allograft vascular bed, the only currently definitive therapy requires re-transplantation. Nevertheless, as we better understand the pathogenesis and critical mediators of these lesions, pharmacological advances can be anticipated. Other articles in this thematic review series focus on the specifics of the inciting injury, the cytokines and chemokines that drive TV development, and the nature of the recruited cells in TV lesions, as well as the pathogenic similarities between TV and other vascular lesions such as atherosclerosis. This review focuses on the mechanisms of vascular wall remodeling in TV, including the intimal accumulation of smooth muscle–like cells and associated extracellular matrix, medial smooth muscle cell degeneration, and adventitial fibrosis. A brief overview highlights the aneurysmal changes that can accrue when vessel wall inflammation has a cytokine profile distinct from the typical proinflammatory interferon-–dominated milieu.
Key Words: transplant vasculopathy • intimal hyperplasia • smooth muscle cells • negative remodeling
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