1996 Fiscal Year Final Research Report Summary
Local angiotensin II formations in human artery desease
| Project/Area Number |
07670826
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Fukuoka University |
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Principal Investigator |
KINOSHITA Akio School of Medicine, 2nd Internal Med. Fukuoka University lecture, 医学部・第二内科, 講師 (40258546)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Chymase / ACE / angiotensin II / human / atherosclerosis / aneurysm |
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| Research Abstract |
Objective : Angiotensin II is generated in human heart not only by angiotensin I converting enzyme (ACE) but also by chymase which derive from mast cell. (ACE : chymase=20 : 75) Mast cells accumulate in aortic aortic aneurysm and atherosclerotic regions. We examined the total amount of Ang II production and ACE/chymase activity ratio in normal aorta and atherosclerosis (AT) as well as aneurysmal regions of human aorta.
Design and methods : Tissues of human aorta (n=8). AT (n=6) and aortic aneurysm (n=4) were obtained from autopsy (within 12 hour after death from patients in whom ACE inhibitor was not used) or operative samples. Tissues were homogenized and the pellets were resuspended in phosphate buffer (pH7.4). The amount of generated Ang II were examined by HPLC after pellets were incubated with Ang I for 15 min at 37 C in the presence or absence of enzyme inhibitors (10^<-4> M capropril for ACE,10^<-5> M chymostatin for chymase).
Recult : Total Ang II forming activity was increased in AT (4.06(]SY.+-。[)2.7 noml/min mg prot) and aortic aneurysm region (5.1(]SY.+-。[)2.4) compared to nomal aorta (1.11(]SY.+-。[)0.5). As for ang I to II conversion, ACE activity was 6% in normal aorta, 5.5% in AT and 0.4% in aortic aneurysm. On the other hand, chymase like activity was 84.5,90.7 and 94.5% respectively. There was significant difference (p<0.05) in chymase activity between normal aorta and aortic aneurysm.
Conclusions : 1) Aortic Ang I conversion activity was remarkably increased in human artery disease. 2) The majority of it derived from chymase which may be responsible for Ang II production in atherosclerotic region.
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