Format

Send to

Choose Destination
Circ J. 2010 Aug;74(8):1518-23. Epub 2010 Jul 17.

Heparin cofactor II attenuates vascular remodeling in humans and mice.

Author information

1
Department of Medicine and Bioregulatory Sciences, The University of Tokushima, Graduate School of Health Biosciences, Tokushima, Japan. aihara@clin.med.tokushima-u.ac.jp

Abstract

Heparin cofactor II (HCII), a serine protease inhibitor (serpin), inactivates thrombin action in the subendothelial layer of the vascular wall. Because a congenitally HCII-deficient patient has been shown to have multiple atherosclerotic lesions, it is hypothesized that HCII plays a pivotal role in the development of vascular remodeling, including atherosclerosis. To clarify this issue, 3 clinical studies concerning plasma HCII activity and atherosclerosis were carried out, and results demonstrated that a higher incidence of in-stent restenosis after percutaneous coronary intervention, maximum carotid arterial plaque thickness, and prevalence of peripheral arterial disease occurred in subjects with low plasma HCII activity. Furthermore, HCII-deficient mice were generated by a gene targeting method to determine the mechanism of the vascular protective action of HCII. Because HCII(-/-) mice were embryonically lethal, we used HCII(+/-) mice and found that they manifested augmentation of intimal hyperplasia and increased thrombosis after cuff or wire injury to the femoral arteries. HCII(+/-) mice with vascular injury showed augmentation of inflammatory cytokines and chemokines and oxidative stress. These abnormal phenotypes of vascular remodeling observed in HCII(+/-) mice were almost restored by human HCII protein supplementation. HCII protects against vascular remodeling, including atherosclerosis, in both humans and mice, and plasma HCII activity might be a predictive biomarker and novel therapeutic target for the prevention of cardiovascular diseases.

PMID:
20671370
DOI:
10.1253/circj.cj-10-0577
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for J-STAGE, Japan Science and Technology Information Aggregator, Electronic
Loading ...
Support Center