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J Thorac Cardiovasc Surg 2004;128:552-561
© 2004 The American Association for Thoracic Surgery

Surgery for acquired cardiovascular disease

Clinical pulmonary autograft valves: Pathologic evidence of adaptive remodeling in the aortic site

^a Department of Pathology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass, USA
^b Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass, USA
^c Cardiac, Thoracic and Vascular Surgery, Inc, St Louis, Mo, USA
^d Cardiac Surgery Department, The Children's Hospital, University of Colorado Health Sciences Center, Denver, Colo, USA
^e Department of Cardiovascular Surgery, Children's Hospital, Harvard Medical School, Boston, Mass, USA
^f Harvard-MIT Division of Health Sciences and Technology (HST), Harvard Medical School, Boston, Mass, USA

Received for publication November 20, 2003; revisions received March 22, 2004; accepted for publication April 19, 2004.

^* Address for reprints: Frederick J. Schoen, MD, PhD, Department of Pathology, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA
fschoen{at}partners.org

OBJECTIVE: We studied the pathologic features, cellular phenotypes, and matrix remodeling of clinical pulmonary-to-aortic valve transplants functioning up to 6 years.

METHODS: Nine autografts and associated vascular walls early (2-10 weeks) and late (3-6 years) postoperatively were examined by using routine morphologic methods and immunohistochemistry. In 4 cases autograft and homograft cusps were obtained from the same patients.

RESULTS: Autografts had near-normal trilaminar cuspal structure and collagen architecture and viable valvular interstitial and endothelial cells throughout the time course. In contrast, cusps of homografts used to replace the pulmonary valves in the same patients were devitalized. In early autograft explants, 19.3% ± 2.4% of cuspal interstitial cells were myofibroblasts expressing -actin. In contrast, myofibroblasts comprised only 6.0% ± 1.1% of cells in late explants and 2.5% ± 0.4% and 4.6% ± 0.8% of cells in normal pulmonary and aortic valves, respectively (P < .05). In early autografts only 12.0% ± 4.6% of endothelial cells expressed the systemic arterial endothelial cell marker EphrinB2, whereas later explants had 85.6% ± 5.4% of endothelial cells expressing EphrinB2 (P < .05). In early autografts 43.8% ± 8.8% of interstitial cells expressed metalloproteinase 13, whereas late autografts had 11.4% ± 2.7% of interstitial cells expressing matrix metalloproteinase 13 (P < .05). Collagen content in autografts was comparable with that of normal valves and was higher than that seen in homograft valves (P < .005). However, autograft walls were damaged, with granulation tissue (early) and scarring, with focal loss of normal smooth muscle cells, elastin, and collagen (late).

CONCLUSIONS: The structure of pulmonary valves transplanted to the systemic circulation evolved toward that of normal aortic valves. Key processes in this remodeling included onset of a systemic endothelial cell phenotype and reversible plasticity of fibroblast-like valvular interstitial cells to myofibroblasts.

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