Human plasminogen kringle1-5 reduces atherosclerosis and neointima formation in mice by suppressing the inflammatory signaling pathway

P. C. Chang, H. L. Wu, H. C.H. Lin, K. C. Wang, G. Y. Shi

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Background: Activation of vascular endothelial cells plays an important role in atherogenesis and plaque instability. Recent research has demonstrated that late-stage inhibition of plaque angiogenesis by angiostatin (kringle 1-4) reduces macrophage accumulation and slows the progression of advanced atherosclerosis. Kringle 1-5 (K1-5) is a variant of angiostatin that contains the first five kringle domains of plasminogen. Objective: To investigate whether K1-5 has an inhibitory effect on early-stage atherosclerosis, using the apolipoprotein E (ApoE)-deficient mouse model and a carotid artery ligation model. Methods: ApoE-deficient mice received K1-5 treatment for 4 weeks, and the severity of aortic atherosclerosis was measured. In the ligation model, the left common carotid arteries of C57BL/6 mice were ligated near the carotid bifurcation, and the mice received K1-5 for 4 weeks. Human umbilical vein endothelial cells were pretreated with K1-5 before tumor necrosis factor-α (TNF-α) treatment to explore the anti-inflammatory effect of K1-5. Results: The areas of the lesion in the aortas of ApoE-deficient mice that received K1-5 treatment were notably decreased, and the formation of carotid neointima in the C57BL/6 mice was decreased by treatment with K1-5. Expression of TNF-α-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 was inhibited by K1-5 treatment, possibly via downregulation of translocation of nuclear factor-γB and expression of reactive oxygen species. Conclusions: K1-5 reduced atherosclerosis and neointima formation in mice, possibly through inhibition of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression in endothelial cells.

Original languageEnglish
Pages (from-to)194-201
Number of pages8
JournalJournal of Thrombosis and Haemostasis
Volume8
Issue number1
DOIs
Publication statusPublished - 2010 Jan

All Science Journal Classification (ASJC) codes

  • Hematology

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