Role of PAPP-A in Atherosclerosis

Using specific monoclonal antibodies, we identified abundant staining for PAPP-A in eroded and ruptured plaques from human arterial specimens. The most intense staining for PAPP-A was at the inflammatory shoulder of the ruptured plaques containing smooth muscle cells and activated macrophages. There was little or no staining for PAPP-A in stable plaques. Our overall hypothesis is that PAPP-A is a key regulatory factor in the vascular response to injury leading to atherosclerosis and promoting plaque vulnerability. Experiments are underway to determine the underlying mechanisms for elevated PAPP-A in vulnerable plaque using human tissue and cell models. In addition, we are determining the effect of PAPP-A deficiency and of targeted PAPP-A overexpression on the development and progression of atherosclerotic plaque in mice on an apolipoprotein E-null background. This project seeks to gain a better understanding of PAPP-A and the IGF system in the fundamental biology of cardiovascular disease, and should establish PAPP-A as a therapeutic target in atherosclerosis.

PAPP-A Human Atherosclerotic Plaque
  • PAPPA-A - Human Atherosclerotic Plaque
    Ruptured

    Ruptured

  • PAPPA-A - Human Atherosclerotic Plaque
    Eroded

    Eroded

  • PAPPA-A - Human Atherosclerotic Plaque
    Eroded

    Eroded

  • PAPPA-A - Human Atherosclerotic Plaque
    Stable

    Stable