Jose Antonio Alvarado-Moreno1, Rubicel Hernandez-Lopez2, Antonieta Chavez-Gonzalez3, Mervin C Yoder4, Rosalva Rangel-Corona5, Irma Isordia-Salas6, Jesus Hernandez-Juarez7, Arturo Cerbulo-Vazquez8, Marco Antonio Gonzalez-Jimenez9, Abraham Majluf-Cruz10. 1. Unidad de Investigacion Medica en Trombosis, Hemostasia y Aterogenesis, IMSS, Gabriel Mancera 222, Col. Del Valle, CP 03100 Mexico City, Mexico. Electronic address: alvarado_m01@yahoo.com.mx. 2. Unidad de Investigacion Medica en Trombosis, Hemostasia y Aterogenesis, IMSS, Gabriel Mancera 222, Col. Del Valle, CP 03100 Mexico City, Mexico. Electronic address: rubicel1981@hotmail.com. 3. Unidad de Investigacion Medica en Enfermedades Oncologicas, IMSS, Av. Cuauhtemoc 330, Col. Doctores, CP 06700 Mexico City, Mexico. Electronic address: achavez_g@yahoo.com.mx. 4. Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut Street, R4-W125, Indianapolis, IN 46202, USA. Electronic address: myoder@iupui.edu. 5. Laboratorio de Oncología Celular, L-4P.B, UMIE-Z, FES-Zaragoza, UNAM, Batalla 5 de Mayo s/n Esq. Fuerte de Loreto, Col. Ejercito de Oriente. C.P. 09230 Mexico City, Mexico. Electronic address: rancor@unam.mx. 6. Unidad de Investigacion Medica en Trombosis, Hemostasia y Aterogenesis, IMSS, Gabriel Mancera 222, Col. Del Valle, CP 03100 Mexico City, Mexico. Electronic address: irmaisordia@yahoo.com.mx. 7. Unidad de Investigacion Medica en Trombosis, Hemostasia y Aterogenesis, IMSS, Gabriel Mancera 222, Col. Del Valle, CP 03100 Mexico City, Mexico. Electronic address: jhdz0912@gmail.com. 8. Hospital de la Mujer, Division de Enseñanza e Investigacion, Salvador Diaz Miron 374, Col. Santo Tomas, Delegacion Miguel Hidalgo, CP 11340 Mexico City, Mexico. Electronic address: cerbulo@hotmail.com. 9. Departamento de Biologia Celular, Instituto Nacional de Perinatologia, Torre de Investigacion, Montes Urales #800 Lomas Virreyes, CP11000 Mexico City, Mexico. Electronic address: marantogo6@hotmail.com. 10. Unidad de Investigacion Medica en Trombosis, Hemostasia y Aterogenesis, IMSS, Gabriel Mancera 222, Col. Del Valle, CP 03100 Mexico City, Mexico. Electronic address: amajlufc@gmail.com.
Abstract
INTRODUCTION: Endothelial cells (ECs) are an important component of the blood coagulation system because it maintains blood fluid. Because in patients with venous thromboembolic disease (VTD) a thrombophilic condition is not found sometimes, we investigated if endothelial colony-forming cells (ECFCs) from these patients have biological and functional abnormalities. PATIENTS AND METHODS: Human mononuclear cells (MNCs) were obtained from peripheral blood from patients with VTD and controls to obtain ECFCs. These cells were assayed for their immunophenotype and electron microscopy characteristics and their ability to form capillary-like structures and to produce pro-inflammatory and pro-angiogenic cytokines and reactive oxygen species (ROS). RESULTS: ECFCs appeared at 7 and 21 days of culture in VTD patients and controls, respectively. ECFCs increased 8-fold in patients and emerged 1 week earlier. No differences in the size of the colonies of ECFCs were found. Numbers and time of appearance of ECFCs was different between groups. ECFC-derived ECs (ECFC-ECs) of both groups expressed CD31, CD34, CD146, and CD-309 but none expressed CD45, CD14, or CD90. Interest CD34 was highly expressed in ECFC-ECs from patients. In both groups, ECFC-ECs showed similar capacity to form capillary-like structures but ECFC-ECs from patients had significant abnormalities in the mitochondrial membrane. We found a significant increase in ROS production in ECFC-ECs from patients. There were significant differences in cytokine profiles between VTD patients and controls. CONCLUSIONS: We found a dysfunctional state in ECFC from VTD patients resembling some characteristics of dysfunctional ECs. These findings may help to understand some pathophysiological aspects of VTD.
INTRODUCTION: Endothelial cells (ECs) are an important component of the blood coagulation system because it maintains blood fluid. Because in patients with venous thromboembolic disease (VTD) a thrombophilic condition is not found sometimes, we investigated if endothelial colony-forming cells (ECFCs) from these patients have biological and functional abnormalities. PATIENTS AND METHODS: Human mononuclear cells (MNCs) were obtained from peripheral blood from patients with VTD and controls to obtain ECFCs. These cells were assayed for their immunophenotype and electron microscopy characteristics and their ability to form capillary-like structures and to produce pro-inflammatory and pro-angiogenic cytokines and reactive oxygen species (ROS). RESULTS: ECFCs appeared at 7 and 21 days of culture in VTD patients and controls, respectively. ECFCs increased 8-fold in patients and emerged 1 week earlier. No differences in the size of the colonies of ECFCs were found. Numbers and time of appearance of ECFCs was different between groups. ECFC-derived ECs (ECFC-ECs) of both groups expressed CD31, CD34, CD146, and CD-309 but none expressed CD45, CD14, or CD90. Interest CD34 was highly expressed in ECFC-ECs from patients. In both groups, ECFC-ECs showed similar capacity to form capillary-like structures but ECFC-ECs from patients had significant abnormalities in the mitochondrial membrane. We found a significant increase in ROS production in ECFC-ECs from patients. There were significant differences in cytokine profiles between VTD patients and controls. CONCLUSIONS: We found a dysfunctional state in ECFC from VTD patients resembling some characteristics of dysfunctional ECs. These findings may help to understand some pathophysiological aspects of VTD.
Authors: Jason A Collett; Purvi Mehrotra; Allison Crone; W Christopher Shelley; Mervin C Yoder; David P Basile Journal: Am J Physiol Renal Physiol Date: 2017-02-22
Authors: Ashay D Bhatwadekar; Yaqian Duan; Maria Korah; Jeffrey S Thinschmidt; Ping Hu; Sameer P Leley; Sergio Caballero; Lynn Shaw; Julia Busik; Maria B Grant Journal: Vision Res Date: 2017-10-31 Impact factor: 1.984