PAPP-A and the IGF system in Atherosclerosis - What's Up, What's Down?

Lasse Bach Steffensen, Cheryl A Conover, Claus Oxvig*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase with a well-established role in releasing bioactive insulin-like growth factor 1 (IGF1) from IGF binding protein 2, -4 and -5 by proteolytic processing of these. The IGF system has repeatedly been suggested to be involved in the pathology of atherosclerosis, and both PAPP-A and IGF1 are proposed biomarkers and therapeutic targets for this disease. Several experimental approaches based on atherosclerosis mouse models have been undertaken to obtain causative and mechanistic insight to the role of these molecules in atherogenesis. However, reports seem conflicting. The literature suggests that PAPP-A is detrimental, while IGF1 is beneficial. This raises important questions that need to be addressed. Here we summarize the various studies and discuss potential underlying explanations for this seemingly inconsistency with the objective of better understanding complexities and limitations when manipulating the IGF system in mouse models of atherosclerosis. A debate clarifying what's up and what's down is highly warranted going forward with the ultimate goal of improving atherosclerosis therapy by targeting the IGF system.

Original languageEnglish
JournalAmerican Journal of Physiology: Heart and Circulatory Physiology
Volume317
Issue number5
Pages (from-to)H1039-H1049
ISSN0363-6135
DOIs
Publication statusPublished - 1. Nov 2019

Keywords

  • IGF system
  • PAPP-A
  • atherosclerosis
  • mouse models
  • Signal Transduction
  • Humans
  • Arteries/metabolism
  • Plaque, Atherosclerotic
  • Insulin-Like Growth Factor I/metabolism
  • Insulin-Like Growth Factor Binding Proteins/metabolism
  • Atherosclerosis/metabolism
  • Animals
  • Pregnancy-Associated Plasma Protein-A/metabolism
  • Mouse models
  • Atherosclerosis

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