Poly(ADP-ribose) Polymerase 1 (PARP1) in Atherosclerosis: From Molecular Mechanisms to Therapeutic Implications

Suowen Xu, P. Bai, Peter J. Little, Peiqing Liu

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Poly(ADP-ribosyl)ation reactions, carried out by poly(ADP-ribose) polymerases (PARPs/ARTDs), are reversible posttranslational modifications impacting on numerous cellular processes (e.g., DNA repair, transcription, metabolism, or immune functions). PARP1 (EC 2.4.2.30), the founding member of PARPs, is particularly important for drug development for its role in DNA repair, cell death, and transcription of proinflammatory genes. Recent studies have established a novel concept that PARP1 is critically involved in the formation and destabilization of atherosclerotic plaques in experimental animal models and in humans. Reduction of PARP1 activity by pharmacological or molecular approaches attenuates atherosclerotic plaque development and enhances plaque stability as well as promotes the regression of pre-established atherosclerotic plaques. Mechanistically, PARP1 inhibition significantly reduces monocyte differentiation, macrophage recruitment, Sirtuin 1 (SIRT1) inactivation, endothelial dysfunction, neointima formation, foam cell death, and inflammatory responses within plaques, all of which are central to the pathogenesis of atherosclerosis. This article presents an overview of the multiple roles and underlying mechanisms of PARP1 activation (poly(ADP-ribose) accumulation) in atherosclerosis and emphasizes the therapeutic potential of PARP1 inhibition in preventing or reversing atherosclerosis and its cardiovascular clinical sequalae.

Original languageEnglish
Pages (from-to)644-675
Number of pages32
JournalMedicinal Research Reviews
Volume34
Issue number3
DOIs
Publication statusPublished - 2014

Fingerprint

Atherosclerosis
Atherosclerotic Plaques
DNA Repair
Cell Death
Therapeutics
Sirtuin 1
Poly Adenosine Diphosphate Ribose
Neointima
Foam Cells
Poly(ADP-ribose) Polymerases
Post Translational Protein Processing
Adenosine Diphosphate
Poly (ADP-Ribose) Polymerase-1
Monocytes
Animal Models
Macrophages
Pharmacology
Pharmaceutical Preparations
Genes

Keywords

  • ADP ribosylation
  • Atherosclerosis
  • PARP
  • Review
  • SIRT1

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Pharmacology

Cite this

Poly(ADP-ribose) Polymerase 1 (PARP1) in Atherosclerosis : From Molecular Mechanisms to Therapeutic Implications. / Xu, Suowen; Bai, P.; Little, Peter J.; Liu, Peiqing.

In: Medicinal Research Reviews, Vol. 34, No. 3, 2014, p. 644-675.

Research output: Contribution to journalArticle

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