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 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2009 |
|---|---|
| Erschienen: |
2009 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:4 |
|---|---|
| Enthalten in: |
PloS one - 4(2009), 10 vom: 13. Okt., Seite e7430 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Hans, Chetan P [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 12.03.2010 Date Revised 20.10.2021 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1371/journal.pone.0007430 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM19200462X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM19200462X | ||
| 003 | DE-627 | ||
| 005 | 20231223192201.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231223s2009 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1371/journal.pone.0007430 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0640.xml |
| 035 | |a (DE-627)NLM19200462X | ||
| 035 | |a (NLM)19823587 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hans, Chetan P |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Protective effects of PARP-1 knockout on dyslipidemia-induced autonomic and vascular dysfunction in ApoE mice |b effects on eNOS and oxidative stress |
| 264 | 1 | |c 2009 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 12.03.2010 | ||
| 500 | |a Date Revised 20.10.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Apolipoproteins E |2 NLM | |
| 650 | 7 | |a Dietary Fats |2 NLM | |
| 650 | 7 | |a Nitric Oxide Synthase Type II |2 NLM | |
| 650 | 7 | |a EC 1.14.13.39 |2 NLM | |
| 650 | 7 | |a Nitric Oxide Synthase Type III |2 NLM | |
| 650 | 7 | |a EC 1.14.13.39 |2 NLM | |
| 650 | 7 | |a Poly(ADP-ribose) Polymerases |2 NLM | |
| 650 | 7 | |a EC 2.4.2.30 |2 NLM | |
| 700 | 1 | |a Feng, Yumei |e verfasserin |4 aut | |
| 700 | 1 | |a Naura, Amarjit S |e verfasserin |4 aut | |
| 700 | 1 | |a Zerfaoui, Mourad |e verfasserin |4 aut | |
| 700 | 1 | |a Rezk, Bashir M |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Huijing |e verfasserin |4 aut | |
| 700 | 1 | |a Kaye, Alan D |e verfasserin |4 aut | |
| 700 | 1 | |a Matrougui, Khalid |e verfasserin |4 aut | |
| 700 | 1 | |a Lazartigues, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Boulares, A Hamid |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t PloS one |d 2006 |g 4(2009), 10 vom: 13. Okt., Seite e7430 |w (DE-627)NLM167327399 |x 1932-6203 |7 nnns |
| 773 | 1 | 8 | |g volume:4 |g year:2009 |g number:10 |g day:13 |g month:10 |g pages:e7430 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1371/journal.pone.0007430 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 4 |j 2009 |e 10 |b 13 |c 10 |h e7430 | ||