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Semin Thromb Hemost 2011; 37(4): 339-348
DOI: 10.1055/s-0031-1276582
© Thieme Medical Publishers

Heparin Cofactor II: Discovery, Properties, and Role in Controlling Vascular Homeostasis

Jill C. Rau1 , 5 , Jennifer W. Mitchell1 , Yolanda M. Fortenberry1 , 6 , Frank C. Church1 , 2 , 3 , 4
  • 1Department of Pathology and Laboratory Medicine, Chapel Hill, North Carolina
  • 2Department of Pharmacology, Chapel Hill, North Carolina
  • 3Department of Medicine, Chapel Hill, North Carolina
  • 4Department of UNC McAllister Heart Institute, The University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina
  • 5Present address for Dr. Rau is Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada
  • 6Present address for Dr. Fortenberry is Department of Pediatric-Hematology, Johns Hopkins University School of Medicine, Baltimore, Maryland
Further Information

Publication History

Publication Date:
30 July 2011 (online)

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ABSTRACT

Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) found in high concentrations in human plasma. Despite its discovery >30 years ago, its physiological function is still poorly understood. It is known to inhibit thrombin, the predominant coagulation protease, and HCII-thrombin complexes have been found in plasma, yet it is thought to contribute little to normal hemostasis. However, thrombin has several other physiological functions, and therefore many biological roles for HCII need consideration. The unique structure and mechanism of action of HCII have helped guide our understanding of HCII. In particular, HCII binds many glycosaminoglycans (GAGs) such as heparin and heparin sulfate as well as several different polyanions to enhance its inhibition of thrombin. Distinctly, HCII is able to use the GAG dermatan sulfate for accelerated thrombin inhibition. Dermatan sulfate is found in high concentrations in the walls of blood vessels as well as in placental tissue. This knowledge has led to research indicating that HCII may play a protective role in atherosclerosis and placental thrombosis. Additionally, pharmaceuticals are being developed that use the dermatan sulfate activation of HCII for anticoagulation. Although much research is still needed to fully understand HCII, this humble protein may have significant impact in our medical future. This article reviews the laboratory history, protein characteristics, structure–activity relationships, protease inhibition, physiological function, and medical relevance of HCII in hopes of regenerating interest in this sometimes forgotten serpin.

KEYWORDS

Heparin cofactor II - serpin - thrombin - dermatan sulfate - heparin

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Frank C ChurchPh.D. 

Department of Pathology and Laboratory Medicine, Campus Box 7035, 932 Mary Ellen Jones Building

The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7035

Email: fchurch@email.unc.edu

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