Stem cell origins of intimal cells in graft arterial disease |
| |
Authors: | Koichi Shimizu Richard N Mitchell |
| |
Institution: | (1) Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Avenue, EBRC 515, 02115 Boston, MA, USA |
| |
Abstract: | Long-term solid organ allografts develop diffuse arterial intimal lesions (graft arterial disease GAD]), consisting of smooth
muscle cells (SMCs), extracellular matrix, and admixed mononuclear leukocytes. Although the exact mechanisms are unknown,
alloresponses likely induce inflammatory cells and/or dysfunctional vascular wall cells to secrete growth factors that promote
SMC intimal recruitment, proliferation, and matrix synthesis. GAD eventually culminates in vascular stenosis and ischemic
graft failure. Although prior work demonstrated that the endothelium and medial SMCs and the vast majority of endothelial
cells (ECs) lining GAD lesions in cardiac allografts are derived from donors, the intimal SMC origin could not be determined.
Recent reports suggest that intimal lesions in allograft vessels may also contain host-derived ECs and SMCs. In light of these
findings, it is noteworthy that subpopulations of bone marrow and circulating cells have also been shown to differentiate
into ECs and SMCs. Here we review recent developments in the understanding of vascular wall cell recruitment that are forcing
a re-evaluation of the pathogenic mechanisms underlying GAD, as well as those occurring in more “conventional” atherosclerosis.
The demonstration of the host origin of intimal SMCs in GAD lays the groundwork for future interventions where therapeutic
genes or drugs may be targeted not to donor medial SMCs, but rather to recipient SM precursor cells. |
| |
Keywords: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|