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 wal...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 α-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 cellmarker EphrinB2,whereas later explants had 85.6%±5.4%of endothelial cells expressing EphrinB2(P< .05). In early autografts 43.0%±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.展开更多
文摘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 α-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 cellmarker EphrinB2,whereas later explants had 85.6%±5.4%of endothelial cells expressing EphrinB2(P< .05). In early autografts 43.0%±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.
