Impaired Endothelial Regeneration Through Human Parvovirus B19-Infected Circulating Angiogenic Cells in Patients With Cardiomyopathy
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Impaired Endothelial Regeneration Through Human Parvovirus B19-Infected Circulating Angiogenic Cells in Patients With Cardiomyopathy. / Schmidt-Lucke, Caroline; Zobel, Thomas; Schrepfer, Sonja; Kuhl, Uwe; Wang, Dong; Klingel, Karin; Becher, Peter Moritz; Fechner, Henry; Pozzuto, Tanja; Van Linthout, Sophie; Lassner, Dirk; Spillmann, Frank; Escher, Felicitas; Holinski, Sebastian; Volk, Hans-Dieter; Schultheiss, Heinz-Peter; Tschope, Carsten.
in: J INFECT DIS, Jahrgang 212, Nr. 7, 01.10.2015, S. 1070-1081.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Impaired Endothelial Regeneration Through Human Parvovirus B19-Infected Circulating Angiogenic Cells in Patients With Cardiomyopathy
AU - Schmidt-Lucke, Caroline
AU - Zobel, Thomas
AU - Schrepfer, Sonja
AU - Kuhl, Uwe
AU - Wang, Dong
AU - Klingel, Karin
AU - Becher, Peter Moritz
AU - Fechner, Henry
AU - Pozzuto, Tanja
AU - Van Linthout, Sophie
AU - Lassner, Dirk
AU - Spillmann, Frank
AU - Escher, Felicitas
AU - Holinski, Sebastian
AU - Volk, Hans-Dieter
AU - Schultheiss, Heinz-Peter
AU - Tschope, Carsten
N1 - © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
PY - 2015/10/1
Y1 - 2015/10/1
N2 - Human parvovirus B19 (B19V) is a common pathogen in microvascular disease and cardiomyopathy, owing to infection of endothelial cells. B19V replication, however, is almost restricted to erythroid progenitor cells (ErPCs). Endothelial regeneration attributable to bone marrow-derived circulating angiogenic cells (CACs) is a prerequisite for organ function. Because of many similarities of ErPCs and CACs, we hypothesized that B19V is a perpetrator of impaired endogenous endothelial regeneration. B19V DNA and messenger RNA from endomyocardial biopsy specimens, bone marrow specimens, and circulating progenitor cells were quantified by polymerase chain reaction analysis. The highest B19V DNA concentrations were found in CD34(+)KDR(+) cells from 17 patients with chronic B19V-associated cardiomyopathy. B19V replication intermediates could be detected in nearly half of the patients. Furthermore, chronic B19V infection was associated with impaired endothelial regenerative capacity. B19V infection of CACs in vitro resulted in expression of transcripts encoding B19V proteins. The capsid protein VP1 was identified as a novel inducer of apoptosis, as were nonstructural proteins. Inhibition studies identified so-called death receptor signaling with activation of caspase-8 and caspase-10 to be responsible for apoptosis induction. B19V causally impaired endothelial regeneration with spreading of B19V in CACs in an animal model in vivo. We thus conclude that B19V infection and damage to CACs result in dysfunctional endogenous vascular repair, supporting the emergence of primary bone marrow disease with secondary end-organ damage.
AB - Human parvovirus B19 (B19V) is a common pathogen in microvascular disease and cardiomyopathy, owing to infection of endothelial cells. B19V replication, however, is almost restricted to erythroid progenitor cells (ErPCs). Endothelial regeneration attributable to bone marrow-derived circulating angiogenic cells (CACs) is a prerequisite for organ function. Because of many similarities of ErPCs and CACs, we hypothesized that B19V is a perpetrator of impaired endogenous endothelial regeneration. B19V DNA and messenger RNA from endomyocardial biopsy specimens, bone marrow specimens, and circulating progenitor cells were quantified by polymerase chain reaction analysis. The highest B19V DNA concentrations were found in CD34(+)KDR(+) cells from 17 patients with chronic B19V-associated cardiomyopathy. B19V replication intermediates could be detected in nearly half of the patients. Furthermore, chronic B19V infection was associated with impaired endothelial regenerative capacity. B19V infection of CACs in vitro resulted in expression of transcripts encoding B19V proteins. The capsid protein VP1 was identified as a novel inducer of apoptosis, as were nonstructural proteins. Inhibition studies identified so-called death receptor signaling with activation of caspase-8 and caspase-10 to be responsible for apoptosis induction. B19V causally impaired endothelial regeneration with spreading of B19V in CACs in an animal model in vivo. We thus conclude that B19V infection and damage to CACs result in dysfunctional endogenous vascular repair, supporting the emergence of primary bone marrow disease with secondary end-organ damage.
KW - Adult
KW - Aged
KW - Animals
KW - Apoptosis
KW - Capsid Proteins/genetics
KW - Cardiomyopathies/complications
KW - Case-Control Studies
KW - Caspase 10/genetics
KW - Cell Line
KW - Endothelial Cells/physiology
KW - Erythema Infectiosum/virology
KW - Erythroid Precursor Cells/physiology
KW - Female
KW - Humans
KW - Male
KW - Mice
KW - Middle Aged
KW - Parvovirus B19, Human/genetics
KW - Regeneration
KW - Signal Transduction
KW - Virus Replication
U2 - 10.1093/infdis/jiv178
DO - 10.1093/infdis/jiv178
M3 - SCORING: Journal article
C2 - 25805750
VL - 212
SP - 1070
EP - 1081
JO - J INFECT DIS
JF - J INFECT DIS
SN - 0022-1899
IS - 7
ER -