Country： Japan

Country： Japan

Grant amount：\4,160,000 （ Direct Cost: \3,200,000 、 Indirect Cost：\960,000 ）

本研究の目的は、障害血管外膜のVasa Vasorum形成異常が動脈硬化プラーク形成に連関しているのかを証明すると共に、Vasa Vasorumの微小血管の形成、成熟化に関わる因子を明らかにすることにある。そのために、冠動脈インターベンションの際にDCA(Directional Coronary Atherectomy)を用いて切除したプラークを採取し、採取したプラークを、組織透明化技術と三次元画像解析法を用いて、プラーク内の微小血管を詳細に評価を行っている。これまで、臨床的にLDLコレステロールが高値の症例で、脂質成分の多いプラークにおいて、微小血管の形状は細く密に集合している傾向があることを確認できている。今後は症例をさらに集めるとともに、Vasa Vasorumの微小血管の形成、成熟化に関わる新規因子を同定し、その発現を評価していく。

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Grant amount：\3,640,000 （ Direct Cost: \2,800,000 、 Indirect Cost：\840,000 ）

This study aims to demonstrate that Ninjurin1 (Ninj1), a novel molecule that regulates vascular maturation, contributes to plaque stabilization through the maturation and stabilization of microvessels (vasa vasorum, VV) that nourish the vessel wall and extend from the outer vascular membrane to the plaque.
In experiments using mice, we confirmed that pericyte-specific knocked out of Ninj1 causes juvenile and fragile VV formation and worsens the pathogenesis of vascular remodeling.
Evaluation using clinical coronary plaque tissue showed that microvessels within the plaque tended to be smaller and denser in patients with high LDL cholesterol levels, suggesting that this vascular infantilization may influence plaque destabilization.

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Grant amount：\4,030,000 （ Direct Cost: \3,100,000 、 Indirect Cost：\930,000 ）

We found that postconditioning with repeated brief ischemia and reperfusion during reperfusion therapy for acute myocardial infarction reduces infarct size, and that the enhanced expression of heat shock protein (HSP) is involved as a mechanism of this reduction. We further developed a heat conditioning method in which hyperthermia, which is expected to enhance HSP expression, is added to postconditioning, and investigated the effect of this method on myocardial salvage. Patients with first acute myocardial infarction were randomly assigned to two groups: a control group and a heat conditioning group. The heat-conditioning group showed increased HSP72 expression in isolated leukocytes, suggesting a high rate of myocardial salvage and possible efficacy.

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Grant amount：\4,290,000 （ Direct Cost: \3,300,000 、 Indirect Cost：\990,000 ）

The first acute myocardial infarction ｐatients were randomly assigned to the control group and the hybrid-conditioning group. In the hybrid-conditioning group, three cycles of remote preconditioning were repeated, with the lower limb being pressurized for 5 minutes and depressurized for 5 minutes. After remote preconditioning, postconditioning was performed 4 cycles of 60s balloon inflation and 30s deflation, and finally the appropriate sized stent was placed. In both groups, blood was collected over time with time before and after reperfusion treatment, and the expression level of HSP72 in the separated leukocytes was quantitatively evaluated. Hybrid-conditioning method was shown to increase the expression of HSP 72, resulting in suppression of reperfusion injury.

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ハイブリッド・コンディショニングによる心筋救済法の開発とHSPを介する機序の解明