The uncoordinated-5 homolog B (UNC5B) receptor increases myocardial ischemia-reperfusion injury.
The UNC5 receptor family are chemorepulsive neuronal guidance receptors with additional functions outside the central nervous system. Previous studies have implicated that the UNC5B receptor influences the migration of leukocytes into sites of tissue inflammation. Given that this process is a critic...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3720625?pdf=render |
| _version_ | 1811228042811408384 |
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| author | David Köhler Ariane Streißenberger Klemens König Tiago Granja Judith M Roth Rainer Lehmann Claudia Bernardo de Oliveira Franz Peter Rosenberger |
| author_facet | David Köhler Ariane Streißenberger Klemens König Tiago Granja Judith M Roth Rainer Lehmann Claudia Bernardo de Oliveira Franz Peter Rosenberger |
| author_sort | David Köhler |
| collection | DOAJ |
| description | The UNC5 receptor family are chemorepulsive neuronal guidance receptors with additional functions outside the central nervous system. Previous studies have implicated that the UNC5B receptor influences the migration of leukocytes into sites of tissue inflammation. Given that this process is a critical step during the pathophysiology of myocardial ischemia followed by reperfusion (IR) we investigated the role of UNC5B during myocardial IR. In initial in-vitro experiments, the functional inhibition of UNC5B resulted in a significant reduction of chemotactic migration of neutrophils. In-vivo, using a model of acute myocardial ischemia in UNC5B(+/-) and wild type (WT) animals, we found a significant reduction of infarct sizes in UNC5B(+/-) animals. This was associated with significantly reduced levels of troponin-I and IL-6 in UNC5B(+/-) mice. The repression of UNC5B using siRNA and the functional inhibition of UNC5B significantly dampened the extent of myocardial IR injury. Following depletion of neutrophils, we were not able to observe any further reduction in infarct size through functional inhibition of UNC5B in WT and UNC5B(+/-) mice. In summary our studies demonstrate an important role for UNC5B during myocardial IR injury, and that UNC5B might be a potential therapeutic target to control reperfusion injury in the future. |
| first_indexed | 2024-04-12T09:51:50Z |
| format | Article |
| id | doaj.art-278c36476b82412b8314bfb2c2cf1db9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T09:51:50Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-278c36476b82412b8314bfb2c2cf1db92022-12-22T03:37:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6947710.1371/journal.pone.0069477The uncoordinated-5 homolog B (UNC5B) receptor increases myocardial ischemia-reperfusion injury.David KöhlerAriane StreißenbergerKlemens KönigTiago GranjaJudith M RothRainer LehmannClaudia Bernardo de Oliveira FranzPeter RosenbergerThe UNC5 receptor family are chemorepulsive neuronal guidance receptors with additional functions outside the central nervous system. Previous studies have implicated that the UNC5B receptor influences the migration of leukocytes into sites of tissue inflammation. Given that this process is a critical step during the pathophysiology of myocardial ischemia followed by reperfusion (IR) we investigated the role of UNC5B during myocardial IR. In initial in-vitro experiments, the functional inhibition of UNC5B resulted in a significant reduction of chemotactic migration of neutrophils. In-vivo, using a model of acute myocardial ischemia in UNC5B(+/-) and wild type (WT) animals, we found a significant reduction of infarct sizes in UNC5B(+/-) animals. This was associated with significantly reduced levels of troponin-I and IL-6 in UNC5B(+/-) mice. The repression of UNC5B using siRNA and the functional inhibition of UNC5B significantly dampened the extent of myocardial IR injury. Following depletion of neutrophils, we were not able to observe any further reduction in infarct size through functional inhibition of UNC5B in WT and UNC5B(+/-) mice. In summary our studies demonstrate an important role for UNC5B during myocardial IR injury, and that UNC5B might be a potential therapeutic target to control reperfusion injury in the future.http://europepmc.org/articles/PMC3720625?pdf=render |
| spellingShingle | David Köhler Ariane Streißenberger Klemens König Tiago Granja Judith M Roth Rainer Lehmann Claudia Bernardo de Oliveira Franz Peter Rosenberger The uncoordinated-5 homolog B (UNC5B) receptor increases myocardial ischemia-reperfusion injury. PLoS ONE |
| title | The uncoordinated-5 homolog B (UNC5B) receptor increases myocardial ischemia-reperfusion injury. |
| title_full | The uncoordinated-5 homolog B (UNC5B) receptor increases myocardial ischemia-reperfusion injury. |
| title_fullStr | The uncoordinated-5 homolog B (UNC5B) receptor increases myocardial ischemia-reperfusion injury. |
| title_full_unstemmed | The uncoordinated-5 homolog B (UNC5B) receptor increases myocardial ischemia-reperfusion injury. |
| title_short | The uncoordinated-5 homolog B (UNC5B) receptor increases myocardial ischemia-reperfusion injury. |
| title_sort | uncoordinated 5 homolog b unc5b receptor increases myocardial ischemia reperfusion injury |
| url | http://europepmc.org/articles/PMC3720625?pdf=render |
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