权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Pathophysiological role of mast cells in cardiovascular diseases.

肥大细胞在心血管疾病中的病理生理作用。

基本信息

批准号：
16590193
负责人：
SHIOTA Naotaka
金额：
$ 1.22万
依托单位：
Shimane University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
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

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590193/
关键词：
mast cell chymase fibrosis cardiovascular disease

项目摘要

1 Mast cells are multi-potent inflammatory cells, which express numerous bioactive factors, such as cytokines, growth factors, and proteases. Mast cells are known to locate in cardiovascular tissues. However, the role of mast cells on the pathogenesis of cardiovascular disease is unknown.2 Our present study attempted to clarify the role of mast cells by analyzing spontaneously hypertensive rats (SHR), which is known to develop genetically hypertension, cardiac hypertrophy, and heart failure.3 Histochemical analysis revealed that the number of mast cells in the cardiovascular tissues of prehypertensive (2 weeks-old) SHR was significantly higher than that of normal control WKY rats, and mast cells are one of the major cells producing TNF-alpha and chymase. Furthermore, TNF-alpha,NF-kB,IL-6,SCF and c-kit mRNA levels in the cardiovascular tissues in SHR were higher than those in WKY rats.4 To further investigate the role of mast cells in SHR, we evaluated the therapeutic effects of a mast cell stabilizer, tranilast, on the development of hypertension in SHR. Montelukast (300 mg/kg/day) was orally administered to SHR for 10 weeks, starting at the age of 2 weeks.5 Treatment with tranilast significantly inhibit the development of hypertension, and decreased the number of mast cells in cardiovascular tissues in SHR. Tranilast also suppressed the perivascular fibrosis and vascular thickening.6 In conclusion, our results support the hypothesis that activation of mast cells in cardiovascular tissues may play a key role in the pathogenesis of cardiovascular diseases.

1肥大细胞是一种多能性炎症细胞，表达多种生物活性因子，如细胞因子、生长因子和蛋白酶。已知肥大细胞位于心血管组织中。然而，肥大细胞在心血管疾病发病机制中的作用尚不清楚。2我们目前的研究试图通过分析自发性高血压大鼠（SHR）来阐明肥大细胞的作用，已知自发性高血压大鼠（SHR）可遗传性地发展高血压、心脏肥大，3组织化学分析显示，高血压前期心血管组织中肥大细胞的数量明显减少，（2周龄）SHR显著高于正常对照WKY大鼠，肥大细胞是产生TNF-α和糜酶的主要细胞之一。此外，SHR心血管组织中TNF-α、NF-kB、IL-6、SCF和c-kit mRNA水平高于WKY大鼠。4为了进一步研究肥大细胞在SHR中的作用，我们评估了肥大细胞稳定剂曲尼司特对SHR高血压发展的治疗作用。从2周龄开始，对SHR口服孟鲁司特（300 mg/kg/天）10周。5曲尼司特治疗显著抑制高血压的发展，并减少SHR心血管组织中肥大细胞的数量。曲尼司特还抑制了血管周围纤维化和血管增厚。6总之，我们的结果支持心血管组织中肥大细胞的活化可能在心血管疾病的发病机制中起关键作用的假设。