on September 3, 2002
Published online before print September 3, 2002, doi: 10.1161/01.CIR.0000031333.86845.DD
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Submitted on May 15, 2002
From the Institute for Pathophysiology (Y.H., H.D) and the Institute for Medical Biology and Human Genetics (M.E.), University of Innsbruck Medical School; the Institute for Biomedical Aging Research (Q.X.), Austrian Academy of Sciences; and the Department of Therapeutic Radiology (M.U.), University Hospital of Innsbruck, Innsbruck, Austria; the Department of Cardiological Sciences (Y.H., F.D., M.M., Q.X.), St George's Hospital Medical School, London, UK; and the Institute of Experimental Immunology (B.L.), University of Zurich, Zurich, Switzerland. * To whom correspondence should be addressed. E-mail: q.xu{at}sghms.ac.uk.
Background—Smooth muscle cell (SMC) accumulation in the intima of vessels is a key event in the pathogenesis of transplant atherosclerosis. The traditional hypothesis that SMCs in the lesion are derived from the media of the donor vessel has been challenged by recent observations, but the cell origin is still not well established. Methods and Results—Here, we use a simplified model of artery allografts in transgenic mice to clearly identify the source of SMCs in transplant atherosclerosis. Aortic segments donated by BALB/c mice allografted to ROSA26 (C57B/6) mice expressing ß-galactosidase (gal) in all tissues showed that neointimal cells derived exclusively from host cells. It was also demonstrated that SMCs of neointimal and atherosclerotic lesions in vessels allografted to mice expressing ß-gal only in SMCs (SM-LacZ) or to apoE-deficient/SM-LacZ mice originated from the recipient, and not donor vessels. Interestingly, bone marrow transplantation of SM-LacZ ß-gal-expressing cells into aortic allograft recipients revealed completely negative ß-gal staining of neointimal and atherosclerotic lesions. However, a population of ß-gal-positive cells in lesions of allografts was observed in chimeric mice with ROSA26 ß-gal-expressing marrow cells. When bone marrow cells from both ROSA26 and SM-LacZ mice were cultured and stimulated with platelet-derived growth factor-BB, Conclusions—Thus, we provide strong evidence that SMCs of neointimal and atherosclerotic lesions in allografts are derived from the recipients and that non-bone marrow-derived progenitor cells are a possible source of SMCs in atherosclerotic lesions.
Revised on July 11, 2002
Accepted on July 11, 2002
Smooth Muscle Cells in Transplant Atherosclerotic Lesions Are Originated From Recipients, but Not Bone Marrow Progenitor Cells
Yanhua Hu MD,
-actin and ß-gal double-positive cells were found, suggesting that bone marrow cells have an ability to differentiate into SMCs.
Key words: transplantation • cells • muscle, smooth • atherosclerosis • genetics
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