THE RAPEUTIC ANGIOGENESIS FOR ISCHEMIC HEART DISEASE

缺血性心脏病的治疗性血管生成

基本信息

批准号：
11670709
负责人：
TAKESHITA Satoshi
金额：
$ 2.3万
依托单位：
TEIKYO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670709/
关键词：
angiogenesis collaterals ischemia

项目摘要

Background : Impaired microvessel development occurs in spontaneously hypertensive rats (SHR) and in patients with essential hypertension. The purpose of this study was to determine whether collateral development is impaired in SHR, and to what extent it is modified by angiotensin-converting enzyme (ACE) inhibition.Methods and Results : Ischemia was induced in the hindlimb of SHR by excision of the femoral artery, after which the animals were randomly assigned to receive low-dose perindopril (0.2 mg/kg/day), high-dose perindopril (2.0 mg/kg/day), or vehicle for 3 weeks. Normotensive Wistar-Kyoto rats (WKY) with femoral artery excision served as a control group. Collateral development was significantly impaired at 4 weeks in SHR versus WKY based on a reduced hindlimb perfusion ratio by laser Doppler imaging (0.86 ± 0.08 versus 1.03 ± 0.09, P < 0.05), and a lower capillary density (364.5 + 43.0 versus 463.8 ± 63.0 /mm^2, P < 0.05). Perindopril administration significantly augmented hindlimb perfusion (low dose : 1.06 ± 0.15 ; high dose : 1.05 ± 0.12, P < 0.05 for both) as well as capillary density (low dose : 494.3 ± 69.8 /mm^2 ; high dose : 543.9 ± 76.9 /mm^2, P < 0.005 for both) in SHR. Conclusions : These findings indicate that collateral development is impaired in SHR and that this impairment can be reversed by ACE inhibition. The angiogenic properties of an ACE inhibitor may benefit patients with essential hypertension presenting with lower limb vascular insufficiency.

背景：微血管发育受损发生在自发性高血压大鼠（SHR）和具有基本高血压的患者中。这项研究的目的是确定SHR中的附带发展是否受到损害，以及血管紧张素转化酶（ACE）抑制作用的改变。方法和结果：在SHR的后肢引起缺血性，因股动脉的惊喜而造成了SHR的后肢，在该动脉中，动物是随机分配了高剂量的/kg（0.2 meg-kg）（0.2 mg-dode perrir kg kg/gg kg（0.2 mg-depy ofder od od od-dep perrill oild/gg）（0.2 mg-deperril（0.2）（2.0 mg/kg/day）或车辆3周。具有股动脉切除术的正常性Wistar-Kyoto大鼠（WKY）是对照组。基于激光多普勒成像的后肢灌注比降低（0.86±0.08 ves 1.03±0.09，p <0.05），以及较低的毛细血管密度（364.5 + 43.0 + 463.0 vors 463.8±63.0 /mmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmm，shr v and wky）的抵押发育显着受损。 Perindopril administration significantly augmented hindlimb perfusion (low dose: 1.06 ± 0.15; high dose: 1.05 ± 0.12, P < 0.05 for both) as well as capillary density (low dose: 494.3 ± 69.8 /mm^2; high dose: 543.9 ± 76.9 /mm^2, P < 0.005 for both) in SHR.结论：这些发现表明，SHR中的附带发展受损，并且这种损害可以通过ACE抑制来逆转。 ACE抑制剂的血管生成特性可能使患有下肢血管功能不全的基本高血压患者受益。