| Project/Area Number |
19K17904
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
|
|---|
| Research Institution | Kanazawa University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2019-04-01 – 2025-03-31
|
| Project Status |
Completed (Fiscal Year 2024)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
|
|---|
| Keywords | IgG4関連動脈/後腹膜疾患 / 動脈硬化 / 症例対照研究 / モデルマウス / IgG4関連動脈/後腹膜疾 |
|---|
| Outline of Research at the Start |
IgG4関連動脈周囲炎/後腹膜線維症の罹患血管では、高率に石灰化や壁在血栓等の動脈硬化性変化を認め、また病変局所で炎症性サイトカインの発現がみられるなど、本病変特有の病態が示唆されている。そこで、当グループで保有している本疾患患者の臨床情報や組織検体、またIgG4関連疾患モデルマウスを用いて、本疾患の病態と動脈硬化病態との関わりを統計学的、また組織学的に明らかにする。また、動脈硬化促進因子への介入が本疾患に及ぼす効果をモデルマウスを用いて組織学的に明らかにし、IgG4関連動脈周囲炎/後腹膜線維症の新たな治療法の開発及び確立のための基礎的な知見を得る。
|
| Outline of Final Research Achievements |
A multi-institutional study was conducted to collect IgG4-RD patients with arterial, retroperitoneal, and cardiac lesions and patients with similar diseases. The findings suggested that periarterial lesions (PA) developed in areas where arteriosclerotic changes were present, and that calcified lesions appeared and worsened in the affected blood vessels during the course of treatment for PA cases, suggesting that PA and arteriosclerosis in the affected area have a mutual effect. In addition, a history of smoking was significantly more prevalent in IgG4-RD than in Mimicker.
In model mice (LAT Y136 mutant mice), renal perivascular lesions were observed in approximately 30-40% of cases, and hydronephrosis was observed in approximately 10% of cases. After unilateral renal ischemia-reperfusion treatment, hydronephrosis was observed in approximately 15% of cases, and there was no clear promotion of vascular lesion formation.
|
| Academic Significance and Societal Importance of the Research Achievements |
臨床的にはIgG4関連動脈病変の病態と動脈硬化病態とが相互に促進的に関連していることが示され、禁煙など動脈硬化促進因子への介入が疾患病態にも影響を及ぼし得ることが示唆された。一方でヒト病変組織においてはM2マクロファージ浸潤やAPRIL発現亢進など、動脈硬化に特徴的と言えない本疾患特有の病態も認められる。モデルマウス(LAT Y136変異マウス)における両病態の解析を進めるために、本マウスにおける効率的な動脈硬化促進の方法を確立することが必要である。
|
