2016 Fiscal Year Final Research Report
The role of leucine-rich alpha2 glycoprotein in cardiac remodeling
Project/Area Number |
15K15052
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
General pharmacology
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Research Institution | Osaka University |
Principal Investigator |
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Project Period (FY) |
2015-04-01 – 2017-03-31
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Keywords | 心筋梗塞 / リモデリング / 血管新生 / マクロファージ / 炎症 |
Outline of Final Research Achievements |
Leucine-rich α2-glycoprotein (LRG) is considered as a biomarker of chronic inflammatory diseases. In this study, we addressed functional roles of LRG in cardiac remodeling after myocardial infarction (MI). The expressions of LRG were upregulated in post-infarct myocardium and observed in heart-infiltrated myeloid cells. To elucidate functional roles of LRG in cardiac remodeling, we generated MI in wild-type (WT) and LRG null (LRG-/-) mice and found that LRG gene ablation aggravated myocardial fibrosis with cardiac dysfunction after MI with decreased capillary density at border zone. Consistently, the expression of apelin receptor was reduced in LRG-/- mice, implying that the impaired angiogenic activity is associated with adverse cardiac remodeling in LRG-/- mice. Moreover, LRG gene ablation suppressed the activation of smad1/5/8, a pro-angiogenic signaling pathway. Thus, our data indicate significant roles of myeloid cells in angiogenesis as well as its molecular mechanism.
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Free Research Field |
循環薬理学
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