Targeted Inhibition of Pregnancy-Associated Plasma Protein-A Activity Reduces Atherosclerotic Plaque Burden in Mice

Cheryl A Conover, Laurie K. Bale, Claus Oxvig

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The metalloproteinase, pregnancy-associated plasma protein-A (PAPP-A), has been implicated in the development of cardiovascular disease in humans and mouse models. In the latter, genetic deletion or overexpression of PAPP-A confirmed a major role for PAPP-A in atherosclerosis. In this study, we tested the hypothesis that targeting PAPP-A proteolytic activity by an inhibitory monoclonal antibody (mAb-PA) reduces atherosclerotic plaque progression. Apolipoprotein E knock-out mice on high-fat diet were treated with mAb-PA or isotype control. Control mice had a 10-fold increase in aortic plaque after 10 weeks. Aortic plaque burden was reduced by ∼70 % in mice treated with mAb-PA (P = 0.0002). Treatment was efficacious even in the face of elevated cholesterol and triglycerides. This study demonstrates proof-of-principle and provides feasibility for a novel therapeutic strategy to inhibit atherosclerotic plaque burden by selective targeting of PAPP-A.

Original languageEnglish (US)
Pages (from-to)77-79
Number of pages3
JournalJournal of Cardiovascular Translational Research
Volume9
Issue number1
DOIs
StatePublished - Feb 1 2016

Fingerprint

Pregnancy-Associated Plasma Protein-A
Atherosclerotic Plaques
High Fat Diet
Metalloproteases
Apolipoproteins E
Hypercholesterolemia
Knockout Mice
Atherosclerosis
Triglycerides
Cardiovascular Diseases
Monoclonal Antibodies

Keywords

  • Atherosclerosis
  • Insulin-like growth factor
  • Monoclonal antibody
  • Pregnancy-associated plasma protein-A

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Genetics
  • Genetics(clinical)
  • Molecular Medicine
  • Pharmaceutical Science

Cite this

Targeted Inhibition of Pregnancy-Associated Plasma Protein-A Activity Reduces Atherosclerotic Plaque Burden in Mice. / Conover, Cheryl A; Bale, Laurie K.; Oxvig, Claus.

In: Journal of Cardiovascular Translational Research, Vol. 9, No. 1, 01.02.2016, p. 77-79.

Research output: Contribution to journalArticle

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N2 - The metalloproteinase, pregnancy-associated plasma protein-A (PAPP-A), has been implicated in the development of cardiovascular disease in humans and mouse models. In the latter, genetic deletion or overexpression of PAPP-A confirmed a major role for PAPP-A in atherosclerosis. In this study, we tested the hypothesis that targeting PAPP-A proteolytic activity by an inhibitory monoclonal antibody (mAb-PA) reduces atherosclerotic plaque progression. Apolipoprotein E knock-out mice on high-fat diet were treated with mAb-PA or isotype control. Control mice had a 10-fold increase in aortic plaque after 10 weeks. Aortic plaque burden was reduced by ∼70 % in mice treated with mAb-PA (P = 0.0002). Treatment was efficacious even in the face of elevated cholesterol and triglycerides. This study demonstrates proof-of-principle and provides feasibility for a novel therapeutic strategy to inhibit atherosclerotic plaque burden by selective targeting of PAPP-A.

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