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Updated: Jun 19, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Protective effects of PARP-1 knockout on dyslipidemia-induced autonomic and vascular dysfunction in ApoE mice:
Chetan P Hans1, Yumei Feng, Amarjit S Naura
1Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
Abstract:
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.
Insights
Poly(ADP-ribose) polymerase-1 (PARP-1) significantly contributes to vascular and autonomic dysfunction in dyslipidemia. Inhibiting PARP-1 in mice models improved cardiovascular function and reduced oxidative stress.
Area of Science:
- Biomedical Science
- Cardiovascular Research
- Molecular Biology
Background:
- Dyslipidemia is linked to vascular dysfunction and autonomic nervous system imbalance.
- Poly(ADP-ribose) polymerase-1 (PARP-1) is implicated in cellular stress responses.
Purpose of the Study:
- To investigate the role of PARP-1 in dyslipidemia-associated vascular and autonomic dysfunction.
- To evaluate the therapeutic potential of PARP-1 inhibition.
Main Methods:
- Apolipoprotein E knockout (ApoE-/-) mice on a high-fat diet were used as an atherosclerosis model.
- Vascular and autonomic functions were assessed using telemetry in conscious mice.
- PARP-1 gene knockout was employed to assess its inhibitory effects.
Main Results:
- PARP-1 plays a critical role in dyslipidemia-induced vascular and autonomic dysfunction.
- PARP-1 gene deletion partially restored baroreflex sensitivity and improved heart rate responses.
- Inhibition of PARP-1 preserved endothelial nitric oxide synthase (eNOS) activity and reduced oxidative stress markers like inducible nitric oxide synthase (iNOS).
Conclusions:
- PARP-1 contributes to vascular and autonomic pathologies in dyslipidemia through oxidative tissue injury.
- PARP-1 gene deletion offers a protective effect by mitigating oxidative damage and normalizing vascular and autonomic functions.
- Maintaining eNOS activity is a potential mechanism for the protective effects of PARP-1 inhibition.
