| Title | Human plasminogen kringle 1-5 reduces atherosclerosis and neointima formation in mice by suppressing the inflammatory signaling pathway. | | Author(s) | Chang PC, Wu HL, Lin HC, Wang KC, Shi GY | | Institution | Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan. | | Source | J Thromb Haemost 2009 Oct 30. | | Abstract | Summary
Background: Activation of vascular endothelial cells (ECs) plays an important role in atherogenesis and plaque instability. Recent research 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 (K(1-5)) is a variant of angiostatin that contains the first five kringle domains of plasminogen.
Objective: To investigate whether K(1-5) has an inhibitory effect on early-stage atherosclerosis using the apolipoprotein E (ApoE)-deficient mice model and a carotid artery ligation model.
Methods: ApoE-deficient mice received K(1-5) 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 K(1-5) for 4 weeks. Human umbilical vein endothelial cells were pretreated with K(1-5) before TNF-alpha treatment to explore the anti-inflammatory effect of K(1-5).
Results: The areas of the lesion in the aortas of ApoE-deficient mice that received K(1-5) treatment were notably decreased, and the formation of carotid neointima in the C57BL/6 mice was decreased by treatment with K(1-5). Expression of TNF-alpha-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 was inhibited by K(1-5) treatment, possibly via down-regulation of translocation of nuclear factor-kappaB and expression of reactive oxygen species.
Conclusions: K(1-5) reduced atherosclerosis and neointima formation in mice, possibly through inhibition of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression in ECs. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19874473 |
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