Skip Navigation



Cardiovascular Research Advance Access [Accepted Manuscript] published online on December 18, 2007
Cardiovascular Research, doi:10.1093/cvr/cvm110
This Article
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
78/1/158    most recent
cvm110v2
cvm110v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by von Lukowicz, T.
Right arrow Articles by Matter, C. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by von Lukowicz, T.
Right arrow Articles by Matter, C. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

PARP1 is required for adhesion molecule expression in atherogenesis

Tobias von Lukowicz1,2, Paul O. Hassa3, Christine Lohmann1,2, Jan Borén4, Vincent Braunersreuther5, François Mach5, Bernhard Odermatt6, Monika Gersbach3, Giovanni G. Camici1,2, Barbara E. Stähli1,2, Felix C. Tanner1,2, Michael O. Hottiger3, Thomas F. Lüscher1,2 and Christian M. Matter1,2,

1 Cardiovascular Research, Institute of Physiology, University of Zurich and Cardiology, Cardiovascular Center, University Hospital Zurich, Switzerland
2 Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland
3 Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Switzerland
4 Wallenberg Laboratory Sahlgrenska Academy at Goteborg University, Goteborg, Sweden
5 Division of Cardiology, University Hospital Geneva, Switzerland
6 Institute of Surgical Pathology, University Hospital Zurich, Switzerland

Address for correspondence: Christian M. Matter, MD Cardiovascular Research, Institute of Physiology, University of Zurich and Cardiology, Cardiovascular Center, University Hospital Zurich Winterthurerstrasse 190, CH-8057 Zurich, Switzerland Email: cmatter{at}physiol.uzh.ch Phone: +41 44 635 6467 Fax: +41 44 635 6827

Aim: Atherosclerosis is the leading cause of death in Western societies and a chronic inflammatory disease. However, the key mediators linking recruitment of inflammatory cells to atherogenesis remain poorly defined. Poly(ADP-ribose) polymerase 1 (PARP1) is a nuclear enzyme that plays a role in acute inflammatory diseases.

Methods: In order to test the role of PARP in atherogenesis, we applied chronic pharmacological PARP inhibition or genetic PARP1 deletion in atherosclerosis-prone apolipoprotein E-deficient mice and measured plaque formation, adhesion molecules, and features of plaque vulnerability.

Results: After 12 weeks of high-cholesterol diet, plaque formation in male apolipoprotein E-deficient mice was decreased by chronic inhibition of enzymatic PARP activity or genetic deletion of PARP1 by 46 or 51 %, respectively (P < 0.05, n ≥ 9). PARP inhibition or PARP1 deletion reduced PARP activity and diminished expression of inducible nitric oxide synthase (iNOS), vascular cell adhesion molecule-1 (VCAM-1), and P- and E-selectin. Furthermore, chronic PARP inhibition reduced plaque macrophage (CD68) and T-cell infiltration (CD3), increased fibrous cap thickness, and decreased necrotic core size and cell death (P < 0.05, n ≥ 6).

Conclusions: Our data provide pharmacological and genetic evidence that endogenous PARP1 is required for atherogenesis in vivo by increasing adhesion molecules with endothelial activation, enhancing inflammation, and inducing features of plaque vulnerability. Thus, inhibition of PARP1 may represent a promising therapeutic target in atherosclerosis.

KEYWORDS Atherosclerosis; PARP; inflammation; macrophages; adhesion molecule

Time for primary review: 20

von Lukowicz: PARP1 is required in atherosclerosis


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.