Protective effects of PARP-1 knockout on dyslipidemia-induced autonomic and vascular dysfunction in ApoE mice: effects on eNOS and oxidative stress.
The aims of this study were to investigate the role of poly(ADP-ribose) polymerase (PARP)-1 in dyslipidemia-associated vascular dysfunction as well as autonomic nervous system dysregulation. Apolipoprotein (ApoE)(-/-) mice fed a high-fat diet were used as a model of atherosclerosis. Vascular and aut...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-10-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2757717?pdf=render |
| _version_ | 1818507163949072384 |
|---|---|
| author | Chetan P Hans Yumei Feng Amarjit S Naura Mourad Zerfaoui Bashir M Rezk Huijing Xia Alan D Kaye Khalid Matrougui Eric Lazartigues A Hamid Boulares |
| author_facet | Chetan P Hans Yumei Feng Amarjit S Naura Mourad Zerfaoui Bashir M Rezk Huijing Xia Alan D Kaye Khalid Matrougui Eric Lazartigues A Hamid Boulares |
| author_sort | Chetan P Hans |
| collection | DOAJ |
| description | The aims of this study were to investigate the role of poly(ADP-ribose) polymerase (PARP)-1 in dyslipidemia-associated vascular dysfunction as well as autonomic nervous system dysregulation. Apolipoprotein (ApoE)(-/-) mice fed a high-fat diet were used as a model of atherosclerosis. Vascular and autonomic functions were measured in conscious mice using telemetry. The study revealed that PARP-1 plays an important role in dyslipidemia-associated vascular and autonomic dysfunction. Inhibition of this enzyme by gene knockout partially restored baroreflex sensitivity in ApoE(-/-) mice without affecting baseline heart-rate and arterial pressure, and also improved heart-rate responses following selective blockade of the autonomic nervous system. The protective effect of PARP-1 gene deletion against dyslipidemia-induced endothelial dysfunction was associated with preservation of eNOS activity. Dyslipidemia induced PARP-1 activation was accompanied by oxidative tissue damage, as evidenced by increased expression of iNOS and subsequent protein nitration. PARP-1 gene deletion reversed these effects, suggesting that PARP-1 may contribute to vascular and autonomic pathologies by promoting oxidative tissue injury. Further, inhibition of this oxidative damage may account for protective effects of PARP-1 gene deletion on vascular and autonomic functions. This study demonstrates that PARP-1 participates in dyslipidemia-mediated dysregulation of the autonomic nervous system and that PARP-1 gene deletion normalizes autonomic and vascular dysfunctions. Maintenance of eNOS activity may be associated with the protective effect of PARP-1 gene deletion against dyslipidemia-induced endothelial dysfunction. |
| first_indexed | 2024-12-10T22:14:48Z |
| format | Article |
| id | doaj.art-8fc1448e202047558e2660f7dc6fce0f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T22:14:48Z |
| publishDate | 2009-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8fc1448e202047558e2660f7dc6fce0f2022-12-22T01:31:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-10-01410e743010.1371/journal.pone.0007430Protective effects of PARP-1 knockout on dyslipidemia-induced autonomic and vascular dysfunction in ApoE mice: effects on eNOS and oxidative stress.Chetan P HansYumei FengAmarjit S NauraMourad ZerfaouiBashir M RezkHuijing XiaAlan D KayeKhalid MatrouguiEric LazartiguesA Hamid BoularesThe aims of this study were to investigate the role of poly(ADP-ribose) polymerase (PARP)-1 in dyslipidemia-associated vascular dysfunction as well as autonomic nervous system dysregulation. Apolipoprotein (ApoE)(-/-) mice fed a high-fat diet were used as a model of atherosclerosis. Vascular and autonomic functions were measured in conscious mice using telemetry. The study revealed that PARP-1 plays an important role in dyslipidemia-associated vascular and autonomic dysfunction. Inhibition of this enzyme by gene knockout partially restored baroreflex sensitivity in ApoE(-/-) mice without affecting baseline heart-rate and arterial pressure, and also improved heart-rate responses following selective blockade of the autonomic nervous system. The protective effect of PARP-1 gene deletion against dyslipidemia-induced endothelial dysfunction was associated with preservation of eNOS activity. Dyslipidemia induced PARP-1 activation was accompanied by oxidative tissue damage, as evidenced by increased expression of iNOS and subsequent protein nitration. PARP-1 gene deletion reversed these effects, suggesting that PARP-1 may contribute to vascular and autonomic pathologies by promoting oxidative tissue injury. Further, inhibition of this oxidative damage may account for protective effects of PARP-1 gene deletion on vascular and autonomic functions. This study demonstrates that PARP-1 participates in dyslipidemia-mediated dysregulation of the autonomic nervous system and that PARP-1 gene deletion normalizes autonomic and vascular dysfunctions. Maintenance of eNOS activity may be associated with the protective effect of PARP-1 gene deletion against dyslipidemia-induced endothelial dysfunction.http://europepmc.org/articles/PMC2757717?pdf=render |
| spellingShingle | Chetan P Hans Yumei Feng Amarjit S Naura Mourad Zerfaoui Bashir M Rezk Huijing Xia Alan D Kaye Khalid Matrougui Eric Lazartigues A Hamid Boulares Protective effects of PARP-1 knockout on dyslipidemia-induced autonomic and vascular dysfunction in ApoE mice: effects on eNOS and oxidative stress. PLoS ONE |
| title | Protective effects of PARP-1 knockout on dyslipidemia-induced autonomic and vascular dysfunction in ApoE mice: effects on eNOS and oxidative stress. |
| title_full | Protective effects of PARP-1 knockout on dyslipidemia-induced autonomic and vascular dysfunction in ApoE mice: effects on eNOS and oxidative stress. |
| title_fullStr | Protective effects of PARP-1 knockout on dyslipidemia-induced autonomic and vascular dysfunction in ApoE mice: effects on eNOS and oxidative stress. |
| title_full_unstemmed | Protective effects of PARP-1 knockout on dyslipidemia-induced autonomic and vascular dysfunction in ApoE mice: effects on eNOS and oxidative stress. |
| title_short | Protective effects of PARP-1 knockout on dyslipidemia-induced autonomic and vascular dysfunction in ApoE mice: effects on eNOS and oxidative stress. |
| title_sort | protective effects of parp 1 knockout on dyslipidemia induced autonomic and vascular dysfunction in apoe mice effects on enos and oxidative stress |
| url | http://europepmc.org/articles/PMC2757717?pdf=render |
| work_keys_str_mv | AT chetanphans protectiveeffectsofparp1knockoutondyslipidemiainducedautonomicandvasculardysfunctioninapoemiceeffectsonenosandoxidativestress AT yumeifeng protectiveeffectsofparp1knockoutondyslipidemiainducedautonomicandvasculardysfunctioninapoemiceeffectsonenosandoxidativestress AT amarjitsnaura protectiveeffectsofparp1knockoutondyslipidemiainducedautonomicandvasculardysfunctioninapoemiceeffectsonenosandoxidativestress AT mouradzerfaoui protectiveeffectsofparp1knockoutondyslipidemiainducedautonomicandvasculardysfunctioninapoemiceeffectsonenosandoxidativestress AT bashirmrezk protectiveeffectsofparp1knockoutondyslipidemiainducedautonomicandvasculardysfunctioninapoemiceeffectsonenosandoxidativestress AT huijingxia protectiveeffectsofparp1knockoutondyslipidemiainducedautonomicandvasculardysfunctioninapoemiceeffectsonenosandoxidativestress AT alandkaye protectiveeffectsofparp1knockoutondyslipidemiainducedautonomicandvasculardysfunctioninapoemiceeffectsonenosandoxidativestress AT khalidmatrougui protectiveeffectsofparp1knockoutondyslipidemiainducedautonomicandvasculardysfunctioninapoemiceeffectsonenosandoxidativestress AT ericlazartigues protectiveeffectsofparp1knockoutondyslipidemiainducedautonomicandvasculardysfunctioninapoemiceeffectsonenosandoxidativestress AT ahamidboulares protectiveeffectsofparp1knockoutondyslipidemiainducedautonomicandvasculardysfunctioninapoemiceeffectsonenosandoxidativestress |