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Heparin cofactor II inhibits arterial thrombosis after endothelial injury.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2002 Jan; Vol. 109 (2), pp. 213-9. - Publication Year :
- 2002
-
Abstract
- Heparin cofactor II (HCII) is a plasma protein that inhibits thrombin rapidly in the presence of dermatan sulfate, heparan sulfate, or heparin. HCII has been proposed to regulate coagulation or to participate in processes such as inflammation, atherosclerosis, and wound repair. To investigate the physiologic function of HCII, about 2 kb of the mouse HCII gene, encoding the N-terminal half of the protein, was deleted by homologous recombination in embryonic stem cells. Crosses of F1 HCII(+/-) animals produced HCII(-/-) offspring at the expected mendelian frequency. Biochemical assays confirmed the absence of dermatan sulfate-dependent thrombin inhibition in the plasma of HCII(-/-) animals. Crosses of HCII(-/-) animals produced litters similar in size to those obtained from heterozygous matings. At 1 year of age, HCII-deficient animals were grossly indistinguishable from their wild-type littermates in weight and survival, and they did not appear to have spontaneous thrombosis or other morphologic abnormalities. In comparison with wild-type animals, however, they demonstrated a significantly shorter time to thrombotic occlusion of the carotid artery after photochemically induced endothelial cell injury. This abnormality was corrected by infusion of purified HCII but not ovalbumin. These observations suggest that HCII might inhibit thrombosis in the arterial circulation.
- Subjects :
- Animals
Carotid Arteries drug effects
Carotid Arteries pathology
Carotid Arteries physiopathology
Endothelium, Vascular drug effects
Female
Heparin Cofactor II genetics
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Pentobarbital adverse effects
Recombination, Genetic
Regional Blood Flow
Carotid Artery Thrombosis prevention & control
Heparin Cofactor II physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9738
- Volume :
- 109
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 11805133
- Full Text :
- https://doi.org/10.1172/JCI13432