Heparin Cofactor II Attenuates Vascular Remodeling in Humans and Mice

DOI Web Site 被引用文献2件 参考文献78件
  • Aihara Ken-ichi
    Department of Medicine and Bioregulatory Sciences, The University of Tokushima, Graduate School of Health Biosciences

この論文をさがす

抄録

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.  (Circ J 2010; 74: 1518 - 1523)<br>

収録刊行物

  • Circulation Journal

    Circulation Journal 74 (8), 1518-1523, 2010

    一般社団法人 日本循環器学会

被引用文献 (2)*注記

もっと見る

参考文献 (78)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ