BACKGROUND: Circulating progenitor cells (PCs) may play a role in the pathogenesis of cardiac allograft vasculopathy, the leading cause of morbidity and mortality in heart transplantation (HTx). We assessed the relationship between circulating PCs and their incorporation into allografts and coronary microvascular function in HTx. METHODS: PCs were quantified by flow cytometry on the basis of the surface expression of CD34, CD133, and kinase domain receptor (KDR) antigens. Biopsy specimens at 2 different times were examined. Immunohistochemistry for the stem cell marker c-Kit, endothelial PC (EPC) marker KDR, and CD34 was performed in serial sections in all specimens. Cells positive for each marker were counted in all specimen area sections, and the number obtained was corrected by area section. Coronary flow in the left anterior descending coronary artery was detected at rest and during intravenous adenosine by transthoracic echocardiography. Coronary flow reserve (CFR) was the ratio of hyperemic diastolic mean velocity (DMV)/resting DMV. RESULTS: CFR was measured in 29 patients and was abnormal (CFR < 2) in 6 (Group A) and normal in 23 (Group B). CFR was lower in Group A (1.5 ± 0.1 vs 3.3 ± 0.8, p < 0.0001). CD34(+)KDR(+), CD133(+)KDR(+), and CD34(+)CD133(+)KDR(+) cell counts were lower in Group A (p < 0.05). EPCs in biopsy sections tended to be lower in Group A (p = 0.06) and correlated to circulating CD133(+)KDR(+) and CD34(+)CD133(+)KDR(+) (p = 0.003 and p = 0.052, respectively). CONCLUSIONS: EPCs are decreased in the circulation and in the allograft in patients with microvasculopathy. Defective mobilization and engraftment of EPCs may be involved in the pathogenesis of cardiac allograft vasculopathy.

Impaired endothelial progenitor cell recruitment may contribute to heart transplant microvasculopathy.

OSTO, ELENA;CASTELLANI, CHIARA;FADINI, GIAN PAOLO;BAESSO, ILENIA;GAMBINO, ANTONIO;AGOSTINI, CARLO;AVOGARO, ANGELO;GEROSA, GINO;THIENE, GAETANO;ILICETO, SABINO;ANGELINI, ANNALISA;TONA, FRANCESCO
2011

Abstract

BACKGROUND: Circulating progenitor cells (PCs) may play a role in the pathogenesis of cardiac allograft vasculopathy, the leading cause of morbidity and mortality in heart transplantation (HTx). We assessed the relationship between circulating PCs and their incorporation into allografts and coronary microvascular function in HTx. METHODS: PCs were quantified by flow cytometry on the basis of the surface expression of CD34, CD133, and kinase domain receptor (KDR) antigens. Biopsy specimens at 2 different times were examined. Immunohistochemistry for the stem cell marker c-Kit, endothelial PC (EPC) marker KDR, and CD34 was performed in serial sections in all specimens. Cells positive for each marker were counted in all specimen area sections, and the number obtained was corrected by area section. Coronary flow in the left anterior descending coronary artery was detected at rest and during intravenous adenosine by transthoracic echocardiography. Coronary flow reserve (CFR) was the ratio of hyperemic diastolic mean velocity (DMV)/resting DMV. RESULTS: CFR was measured in 29 patients and was abnormal (CFR < 2) in 6 (Group A) and normal in 23 (Group B). CFR was lower in Group A (1.5 ± 0.1 vs 3.3 ± 0.8, p < 0.0001). CD34(+)KDR(+), CD133(+)KDR(+), and CD34(+)CD133(+)KDR(+) cell counts were lower in Group A (p < 0.05). EPCs in biopsy sections tended to be lower in Group A (p = 0.06) and correlated to circulating CD133(+)KDR(+) and CD34(+)CD133(+)KDR(+) (p = 0.003 and p = 0.052, respectively). CONCLUSIONS: EPCs are decreased in the circulation and in the allograft in patients with microvasculopathy. Defective mobilization and engraftment of EPCs may be involved in the pathogenesis of cardiac allograft vasculopathy.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/2443185
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