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PAPP-A and the IGF system in atherosclerosis: what's up, what's down?

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  • Lasse B. Steffensen, University of Southern Denmark
  • ,
  • Cheryl A. Conover, Mayo Clinic Rochester, MN
  • ,
  • Claus Oxvig

Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase with a well-established role in releasing bioactive insulin-like growth factor-1 (IGF-1) 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 IGF-1 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 IGF-1 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
Pages (from-to)H1039-H1049
Number of pages11
Publication statusPublished - Nov 2019

    Research areas

  • IGF system, PAPP-A, atherosclerosis, mouse models

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