Crucial role of hyaluronan derived from macrophages in neointimal formation after vascular injury.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26860550
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Shinshu University
• Principal Investigator: KASHIMA Yuichiro 信州大学, 学術研究院医学系(医学部附属病院), 助教 (70545722)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ヒアルロン酸 / 新生内膜肥厚

Outline of Final Research Achievements

Hyaluronan (HA) is a primary component of the extracellular matrix of cells, and it is involved in the pathogenesis of atherosclerosis. HA was found to be expressed in neointimal lesions after wire-mediated vascular injury in mice. Inhibition of HA synthesis using 4-methylumbelliferone markedly inhibited neointimal formation after injury. In vitro experiments revealed that low-molecular-weight HA (LMW-HA) induced macrophages activation, including migration and production of inflammatory cytokines, and reactive oxygen species (ROS). The migration of macrophages were mediated by the CD44/RhoA. Because HA synthase 2 (HAS2) is predominantly expressed in injured arteries, we generated cTg mice that overexpress the murine HAS2 gene specifically in macrophages (cHAS2/CreLys mice) and showed that HA overexpression markedly enhanced neointimal formation after cuff-mediated vascular injury. Macrophages-derived HA promotes neointimal formation after vascular injury.

Free Research Field

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