Identification of putative endothelial progenitor cells (CD34 +CD133+Flk-1+) in endarterectomized tissue of patients with chronic thromboembolic pulmonary hypertension

Weijuan Yao, Amy L. Firth, Richard S. Sacks, Aiko Ogawa, William R. Auger, Peter F. Fedullo, Michael M. Madani, Grace Y. Lin, Naohide Sakakibara, Patricia A. Thistlethwaite, Stuart W. Jamieson, Lewis J. Rubin, Jason Yuan

Research output: Contribution to journalArticle

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Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by a fibrotic thrombus persisting and obliterating the lumen of pulmonary arteries; its pathogenesis remains poorly defined. This study investigates a potential contribution for progenitor cell types in the development of vascular obliteration and remodeling in CTEPH patients. Endarterectomized tissue from patients undergoing pulmonary thromboendarterectomy was collected and examined for the structure and cellular composition. Our data show an organized fibrin network structure in unresolved thromboemboli and intimal remodeling in vascular wall tissues, characterized by smooth muscle α-actin (SM-αA)- positive cell proliferation in proximal regions (adjacent to thromboemboli) and neoangiogenesis/recanalization in distal regions (downstream from thromboemboli). Cells that are positively stained with CD34 and fetal liver kinase-1 (Flk-1) (CD34+Flk-1+) were identified in both the proximal and distal vascular tissues; a subpopulation of CD34 +Flk-1+CD133+ cells were further identified by immunostaining. Triple-positive cells are indicative of a population of putative endothelial progenitor cells or potential colony-forming units of endothelial cells. In addition, inflammatory cells (CD45+) and collagen-secreting cells (procollagen-1+) were detected in the proximal vascular wall. Some of the CD34+ cells in CTEPH cells isolated from proximal regions were also positive for SM-αA. Our data indicate that putative progenitor cell types are present in the neointima of occluded vessels of CTEPH patients. It is possible that the microenvironment provided by thromboemboli may promote these putative progenitor cells to differentiate and enhance intimal remodeling.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume296
Issue number6
DOIs
StatePublished - Jun 2009
Externally publishedYes

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Vascular Endothelial Growth Factor Receptor-2
Pulmonary Hypertension
Stem Cells
Tunica Intima
Blood Vessels
Neointima
Procollagen
Endarterectomy
Cellular Structures
Endothelial Progenitor Cells
Fibrin
Pulmonary Artery
Smooth Muscle
Actins
Thrombosis
Collagen
Endothelial Cells
Cell Proliferation
Lung
Population

Keywords

  • Endarterectomy
  • Pulmonary embolism
  • Vascular remodeling

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Identification of putative endothelial progenitor cells (CD34 +CD133+Flk-1+) in endarterectomized tissue of patients with chronic thromboembolic pulmonary hypertension. / Yao, Weijuan; Firth, Amy L.; Sacks, Richard S.; Ogawa, Aiko; Auger, William R.; Fedullo, Peter F.; Madani, Michael M.; Lin, Grace Y.; Sakakibara, Naohide; Thistlethwaite, Patricia A.; Jamieson, Stuart W.; Rubin, Lewis J.; Yuan, Jason.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 296, No. 6, 06.2009.

Research output: Contribution to journalArticle

Yao, Weijuan ; Firth, Amy L. ; Sacks, Richard S. ; Ogawa, Aiko ; Auger, William R. ; Fedullo, Peter F. ; Madani, Michael M. ; Lin, Grace Y. ; Sakakibara, Naohide ; Thistlethwaite, Patricia A. ; Jamieson, Stuart W. ; Rubin, Lewis J. ; Yuan, Jason. / Identification of putative endothelial progenitor cells (CD34 +CD133+Flk-1+) in endarterectomized tissue of patients with chronic thromboembolic pulmonary hypertension. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2009 ; Vol. 296, No. 6.
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abstract = "Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by a fibrotic thrombus persisting and obliterating the lumen of pulmonary arteries; its pathogenesis remains poorly defined. This study investigates a potential contribution for progenitor cell types in the development of vascular obliteration and remodeling in CTEPH patients. Endarterectomized tissue from patients undergoing pulmonary thromboendarterectomy was collected and examined for the structure and cellular composition. Our data show an organized fibrin network structure in unresolved thromboemboli and intimal remodeling in vascular wall tissues, characterized by smooth muscle α-actin (SM-αA)- positive cell proliferation in proximal regions (adjacent to thromboemboli) and neoangiogenesis/recanalization in distal regions (downstream from thromboemboli). Cells that are positively stained with CD34 and fetal liver kinase-1 (Flk-1) (CD34+Flk-1+) were identified in both the proximal and distal vascular tissues; a subpopulation of CD34 +Flk-1+CD133+ cells were further identified by immunostaining. Triple-positive cells are indicative of a population of putative endothelial progenitor cells or potential colony-forming units of endothelial cells. In addition, inflammatory cells (CD45+) and collagen-secreting cells (procollagen-1+) were detected in the proximal vascular wall. Some of the CD34+ cells in CTEPH cells isolated from proximal regions were also positive for SM-αA. Our data indicate that putative progenitor cell types are present in the neointima of occluded vessels of CTEPH patients. It is possible that the microenvironment provided by thromboemboli may promote these putative progenitor cells to differentiate and enhance intimal remodeling.",
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AU - Firth, Amy L.

AU - Sacks, Richard S.

AU - Ogawa, Aiko

AU - Auger, William R.

AU - Fedullo, Peter F.

AU - Madani, Michael M.

AU - Lin, Grace Y.

AU - Sakakibara, Naohide

AU - Thistlethwaite, Patricia A.

AU - Jamieson, Stuart W.

AU - Rubin, Lewis J.

AU - Yuan, Jason

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N2 - Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by a fibrotic thrombus persisting and obliterating the lumen of pulmonary arteries; its pathogenesis remains poorly defined. This study investigates a potential contribution for progenitor cell types in the development of vascular obliteration and remodeling in CTEPH patients. Endarterectomized tissue from patients undergoing pulmonary thromboendarterectomy was collected and examined for the structure and cellular composition. Our data show an organized fibrin network structure in unresolved thromboemboli and intimal remodeling in vascular wall tissues, characterized by smooth muscle α-actin (SM-αA)- positive cell proliferation in proximal regions (adjacent to thromboemboli) and neoangiogenesis/recanalization in distal regions (downstream from thromboemboli). Cells that are positively stained with CD34 and fetal liver kinase-1 (Flk-1) (CD34+Flk-1+) were identified in both the proximal and distal vascular tissues; a subpopulation of CD34 +Flk-1+CD133+ cells were further identified by immunostaining. Triple-positive cells are indicative of a population of putative endothelial progenitor cells or potential colony-forming units of endothelial cells. In addition, inflammatory cells (CD45+) and collagen-secreting cells (procollagen-1+) were detected in the proximal vascular wall. Some of the CD34+ cells in CTEPH cells isolated from proximal regions were also positive for SM-αA. Our data indicate that putative progenitor cell types are present in the neointima of occluded vessels of CTEPH patients. It is possible that the microenvironment provided by thromboemboli may promote these putative progenitor cells to differentiate and enhance intimal remodeling.

AB - Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by a fibrotic thrombus persisting and obliterating the lumen of pulmonary arteries; its pathogenesis remains poorly defined. This study investigates a potential contribution for progenitor cell types in the development of vascular obliteration and remodeling in CTEPH patients. Endarterectomized tissue from patients undergoing pulmonary thromboendarterectomy was collected and examined for the structure and cellular composition. Our data show an organized fibrin network structure in unresolved thromboemboli and intimal remodeling in vascular wall tissues, characterized by smooth muscle α-actin (SM-αA)- positive cell proliferation in proximal regions (adjacent to thromboemboli) and neoangiogenesis/recanalization in distal regions (downstream from thromboemboli). Cells that are positively stained with CD34 and fetal liver kinase-1 (Flk-1) (CD34+Flk-1+) were identified in both the proximal and distal vascular tissues; a subpopulation of CD34 +Flk-1+CD133+ cells were further identified by immunostaining. Triple-positive cells are indicative of a population of putative endothelial progenitor cells or potential colony-forming units of endothelial cells. In addition, inflammatory cells (CD45+) and collagen-secreting cells (procollagen-1+) were detected in the proximal vascular wall. Some of the CD34+ cells in CTEPH cells isolated from proximal regions were also positive for SM-αA. Our data indicate that putative progenitor cell types are present in the neointima of occluded vessels of CTEPH patients. It is possible that the microenvironment provided by thromboemboli may promote these putative progenitor cells to differentiate and enhance intimal remodeling.

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KW - Pulmonary embolism

KW - Vascular remodeling

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