The annexin A2 system and vascular homeostasis

Vascul Pharmacol. Mar-Jun 2011;54(3-6):59-67. doi: 10.1016/j.vph.2011.03.003. Epub 2011 Mar 29.

Abstract

Optimal fibrin balance requires precisely controlled plasmin generation on the surface of endothelial cells, which line the blood vessel wall. As a co-receptor for plasminogen and tissue plasminogen activator (tPA), which are key factors in plasmin generation, the annexin A2 (A2) complex promotes vascular fibrinolysis. The intracellular A2 complex is a heterotetramer of two A2 monomers and two copies of the associated protein, p11. In response to endothelial cell activation, A2 is phosphorylated by src-kinase, and translocated to the cell surface in a highly regulated manner. Over-expression of A2 is seen in acute promyelocytic leukemia during the early hemorrhagic phase, while high titer antibodies to A2, as in antiphospholipid syndrome or cerebral venous thrombosis, are associated with thrombosis. In experimental hyperhomocysteinemia, moreover, derivatization of A2 by homocysteine leads to intravascular fibrin accumulation and dysangiogenesis, features that phenocopy the Anxa2(-/-) mouse. Exogenous A2 may also offer a novel therapeutic approach to ischemic thrombotic stroke, as administration of A2 in conjunction with conventional tPA-based thrombolytic therapy improved outcome in an animal model. Here, we discuss the role of the A2 system in vascular homeostasis, the molecular interactions that regulate its profibrinolytic activity, and its potential role in the pathogenesis and treatment of vascular disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Annexin A2 / genetics
  • Annexin A2 / metabolism*
  • Annexin A2 / therapeutic use
  • Endothelial Cells / metabolism
  • Fibrin / metabolism*
  • Fibrinolysin / metabolism
  • Fibrinolysis*
  • Gene Expression Regulation
  • Homeostasis
  • Humans
  • Mice
  • Mice, Knockout
  • Thrombolytic Therapy / methods
  • Tissue Plasminogen Activator / therapeutic use
  • Vascular Diseases / drug therapy
  • Vascular Diseases / physiopathology

Substances

  • Annexin A2
  • Fibrin
  • Tissue Plasminogen Activator
  • Fibrinolysin