TIMP-2: an endogenous inhibitor of angiogenesis

Trends Mol Med. 2005 Mar;11(3):97-103. doi: 10.1016/j.molmed.2005.01.007.


Remodeling of the extracellular matrix--regulated by the matrix metalloproteinases (MMPs) and their endogenous inhibitors--is an important component of disease progression in many chronic disease states. Unchecked MMP activity can result in significant tissue damage, facilitate disease progression and is associated with host responses to pathologic injury, such as angiogenesis. The tissue inhibitors of metalloproteinases (TIMPs) have been shown to regulate MMP activity. However, recent findings demonstrate that an MMP-independent effect of TIMP-2 inhibits the mitogenic response of human microvascular endothelial cells to growth factors. This is the first demonstration of a cell-surface signaling receptor for a member of the TIMP family and suggests that TIMP-2 functions to regulate cellular responses to growth factors. These new findings are integrated in a comprehensive model of TIMP-2 function in tissue homeostasis.

Publication types

  • Review

MeSH terms

  • Endothelial Cells / physiology*
  • Extracellular Matrix / metabolism
  • Growth Substances / metabolism
  • Homeostasis / physiology*
  • Humans
  • Metalloproteases / antagonists & inhibitors*
  • Mitosis / physiology*
  • Models, Biological*
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / physiopathology*
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism*


  • Growth Substances
  • Tissue Inhibitor of Metalloproteinase-2
  • Metalloproteases