Studies on visualization of arteriosclerotic lesion using vascular cell-derived vasoactive substances

利用血管细胞源性血管活性物质对动脉硬化病变进行可视化研究

基本信息

批准号：
16390217
负责人：
HIRATA Yasunobu
金额：
$ 8.96万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Endothelial dysfunction is frequently observed in diabetes (DM). However, the detailed mechanism for endothelial dysfunction in DM is still unclear. In DM, it has been reported that cytokines release from adipocytes such as TNF-α and IL-6 is augmented and that they induce vascular inflammation. In this study we study the role of endogenous cytokines in endothelial dysfunction in DM with using semapimod (Sem), an inhibitor of endogenous cytokines release. Male diabetic Zucker rats (12 weeks) were divided into lean (LZ), obese (OZ), and Sem (5mg/kg/day)-treated obese rats (OZ/Sem). After 4 weeks of treatment, endothelium dependent vasodilatory responses of thoracic aorta to acetylcholine (ACh) and adrenomedullin (AM) were examined. Furthermore, induction of Akt phosphorylation (p-Akt) of thoracic aorta which was stimulated with 10^<-7> of AM for 15 min was examined by Western blot analysis. Systolic blood pressure, blood glucose, and triglyceride were higher in OZ rats and Sem treatment had no effect on these parameters. Serum CRP level of OZ rats was higher compared to LZ rats and Sem significantly reduced its level. TNF-α, IL-1β, and IL-6 contents in various tissues were significantly greater in OZ rats than in LZ rats, whereas these increments were suppressed in OZ/Sem rats. Endothelium-dependent vasodilation by ACh and AM was significantly attenuated in OZ rats, and was improved by Sem treatment. Intraperitoneal administration of TNF-α markedly reduced ACh-evoked vasodilation in thoracic aorta of LZ rats. AM-induced p-Akt and cGMP production of thoracic aorta were significantly less in OZ rats compared to LZ rats. However, it was recovered by Sem treatment. In DM, endogenous cytokines play an important role in endothelial dysfunction and inhibition of these cytokines release may improve endothelial dysfunction.

内皮功能障碍经常在糖尿病（DM）中观察到。但是，DM中内皮功能障碍的详细机制尚不清楚。在DM中，据报道，细胞因子从脂肪细胞（例如TNF-α和IL-6）释放出来，并诱导血管感染。在这项研究中，我们研究了内源性细胞因子释放的抑制剂Semapimod（SEM）中内皮功能障碍在DM中的作用。雄性糖尿病扎克大鼠（12周）分为瘦（lz），肥胖（oz）和SEM（5mg/kg/day）处理的肥胖大鼠（OZ/SEM）。经过4周的治疗后，检查了胸主动脉对乙酰胆碱（ACH）和肾上腺肾上腺素（AM）的内皮依赖性血管舒张反应。此外，通过Western blot分析检查了用AM的10^<-7>刺激15分钟的胸主动脉的Akt磷酸化（P-AKT）。 OZ大鼠的收缩压，血糖和甘油三酸酯较高，而SEM治疗对这些参数没有影响。与LZ大鼠相比，血清CRP水平更高，SEM显着降低了其水平。 OZ大鼠的TNF-α，IL-1β和IL-6含量明显大于LZ大鼠，而在OZ/SEM大鼠中，这些增量被抑制。 ACH和AM的内皮依赖性血管舒张在OZ大鼠中显着减弱，并通过SEM治疗改善。 TNF-α的腹膜内给药明显降低了LZ大鼠胸主动脉的ACH诱发血管舒张。与LZ大鼠相比，OZ大鼠的AM诱导的P-AKT和CGMP产生的胸腔主动脉的产生明显少得多。但是，通过SEM治疗将其恢复。在DM中，内源性细胞因子在内皮功能障碍和抑制这些细胞因子释放中起着重要作用，可能会改善内皮功能障碍。

项目成果

期刊论文数量（20）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Highly Sensitive Near-infrared Fluorescence Probes for Nitric Oxide and Their Application to Isolated Organs.

高灵敏一氧化氮近红外荧光探针及其在离体器官中的应用。

DOI：
发表时间：
2005
期刊：
J.Am.Chem.Soc. 127
影响因子：
0
作者：
E.Sasaki;H.Kojima;H.Nishimatsu;Y.Urano;K.Kikuchi;Y.Hirata T.Nagano
通讯作者：
Y.Hirata T.Nagano

Blockade of endogenous cytokines mitigates neointimal formation in obese Zucker rats

DOI：
10.1161/01.cir.0000158482.83179.db
发表时间：
2005-03-22
期刊：
CIRCULATION
影响因子：
37.8
作者：
Takeda, R;Suzuki, E;Hirata, Y
通讯作者：
Hirata, Y

Statins augment collateral growth in response to ischemia but they do not promote cancer and atherosclerosis

DOI：
10.1161/01.hyp.0000126186.29571.41
发表时间：
2004-06-01
期刊：
HYPERTENSION
影响因子：
8.3
作者：
Sata, M;Nishimatsu, H;Nagai, R
通讯作者：
Nagai, R

Age-associated aortic stenosis in apolipoprotein E-deficient mice.

DOI：
10.1016/j.jacc.2005.03.058
发表时间：
2005-07
期刊：
Journal of the American College of Cardiology
影响因子：
24
作者：
Kimie Tanaka;M. Sata;D. Fukuda;Y. Suematsu;N. Motomura;S. Takamoto;Y. Hirata;R. Nagai
通讯作者：
Kimie Tanaka;M. Sata;D. Fukuda;Y. Suematsu;N. Motomura;S. Takamoto;Y. Hirata;R. Nagai

Highly sensitive near-infrared fluorescence probes for nitric oxide and their application to isolated organe.

一氧化氮高灵敏近红外荧光探针及其在分离器官中的应用。