The Role for Cysteine Protease Cathepsin in Left Ventricular Remodeling and Gene Therapy Application.
Project/Area Number |
17590719
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
|
Research Institution | Nagoya University |
Principal Investigator |
CHENG Xianwu Nagoya University, School of Medicine, Research Associate, 医学部, 助手 (30378228)
|
Co-Investigator(Kenkyū-buntansha) |
KAZUYA Masafumi Nagoya University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (10283441)
NAGATA Kouzou Nagoya University, School of Medicine, Associate Professor, 医学部, 助教授 (20378227)
KONDO Takahisa University Hospital, Assistant Professor, 医学部附属病院, 講師 (00303644)
IGUCHI Aakihisa Nagoya University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (20109763)
|
Project Period (FY) |
2005 – 2006
|
Project Status |
Completed (Fiscal Year 2006)
|
Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
Keywords | Ventricular Remodeling / Protease-Cathepsin S / Hypertension / Heart Failure / Cardiomyocyte / Olmesartan / 蛋白質分解酵素-カテプシンS |
Research Abstract |
Background : Cathepsin activation contributes to tissue remodeling in several disease states. The present study tested the hypothesis that cathepsin inhibition prevents LV remodeling and dysfunction in the development of CHF associated with hypertension. Methods and Results : Dahl salt-sensitive rats fed an 8% NaCl diet from age 7 weeks served as a CHF model arbitrarily assigned to three treatment groups at age 12 weeks. The abundance of cathepsin mRNAs and proteins localized in cardiac myocytes (CMCs) and cathepsin-dependent activities were increased in the left ventricle of CHF rats, and were reduced by olmesartan treatment. Olmesartan suppressed the elastic lamina degradation concomitant with decreased local cathepsin S expression in intracoronary smooth muscle cells (SMCs) and restored the ratio of elastin to collagen in CHF rats. Furthermore, olmesartan suppressed not only interleukin-1β expression and macrophage infiltration but also levels of NADPH oxidase components (p22^<phox>, gp91^<phox>, and p47^<phox>) concomitant with decreased NADPH activity and O_2^- production in CHF rats. These were accompanied by improved cardiac fibrosis, stiffness, and dysfunction. Interestingly, all of these improvements were observed by E64d. The antioxidants MnTmPyp and N-acetylcysteine inhibited the H2O2-induced increase in cathepsin expression and elastolytic activity in culture CMCs and SMC. Conclusions : These results suggest that cathepsins are likely to trigger and promote LV remodeling, and that olmesartan-mediated inhibition of angiotensin type1 receptor inhibits cathepsins by suppressing inflammation and oxidative stress, leading to the prevention of cardiac remodeling and dysfunction.
|
Report
(3 results)
Research Products
(28 results)
-
[Journal Article] Mechanisms underlying the impairment of ischemia-induced neovascularization in MMP-2-deficient mice.2007
Author(s)
Cheng XW, Kuzuya M, Nakamura K, Maeda K, Tsuzuki M, Kim W, Sasaki T, Liu Z, Kondo T, Jin H, Numaguchi Y, Okumura K, Yokota T, Iguchi A, Murohara T
-
Journal Title
Circulation Research. 100
Pages: 904-913
Description
「研究成果報告書概要(和文)」より
Related Report
-
-
[Journal Article] Mechanisms underlying the impairment of ischemia-Induced neovascularization in MMP-2-deficient mice.2007
Author(s)
Cheng XW, Kuzuya M, Nakamura K, Maeda K, Tsuzuki M, Kim W, Sasaki T, Li Z, Kondo T, Jin H, Numaguchi Y, Okumura K, Yokota T, Iguchi A, Murohara T
-
Journal Title
Circulation Research. 100
Pages: 904-913
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
[Journal Article] Mechanisms underlying the impairment of ischemia-induced neovascularization in MMP-2-deficient mice.2007
Author(s)
Cheng XW, Kuzuya M, Nakamura K, Maeda K, Tsuzuki M, Kim W, Sasaki T, Liu Z, Kondo T, Jin H, Numaguchi Y, Okumura K, Yokota T, Iguchi A, Murohara T.
-
Journal Title
Circulation Research. 100
Pages: 904-913
Related Report
-
-
-
-
-
-
[Journal Article] Pitavastatin improves cardiac function and survival in association with suppression of the myocardial endothelin system in a rat model of hypertensive heart failure.2006
Author(s)
Saka M, Obata K, Ichihara S, Cheng XW, Kimata H, Takao Nishizawa, Noda K, Izawa H, Nagata K, Murohara T, Yokota M
-
Journal Title
Journal of Cardiovascular Pharmacology 47
Pages: 770-779
Description
「研究成果報告書概要(和文)」より
Related Report
-
[Journal Article] Effect of Green Tea Consumption on Endothelial Function and Circulating Endothelial Progenitor Cells in Chronic Smokers.2006
Author(s)
Kim W, Jeong MH, Cho SH, Yun HY, Chae HJ, Ahn YK, Lee MC, Cheng XW, Kondo T, Murohara T, Kang JC
-
Journal Title
Circulation Journal 70
Pages: 1052-1057
NAID
Description
「研究成果報告書概要(和文)」より
Related Report
-
[Journal Article] A Elastolytic Cathepsin Induction/Activation System Exists in the Rat and Human Myocardium and is Upregulated in Hypertensive Heart Failure.2006
Author(s)
Cheng XW, Obata K, Kzuya M, Izawa H, Nakamura K, Asahi E, Saka M, Kimata T, Nagasaka T, Noda A, Nagata K, Jin H, Shi GP, Iguchi A, Murohara T, Yokota M
-
Journal Title
Hypertension 48
Pages: 979-987
Description
「研究成果報告書概要(和文)」より
Related Report
-
-
[Journal Article] Localization of Cysteine Protease, Cathepsin S, to the Surface of Vascular smooth muscle cells by association with integrin ανβ3.2006
Author(s)
Cheng XW, Kuzuya M, Nakamura K, Di Qun, Liu Z, Sasaki T, Murohara T, Yokota M, Iguchi A
-
Journal Title
American Journal of Pathology 168
Pages: 685-694
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
-
[Journal Article] Pitavastatin improves cardiac function and survival in association with suppression of the myocardial endothelin system in a rat model of hypertensive heart failure.2006
Author(s)
Saka M, Obata K, Ichihara S, Cheng XW, Kimata H, Takao N, Noda K, Izawa H, Nagata K, Murohara T, Yokota M.
-
Journal Title
Journal of Cardiovascular Pharmacology 47
Pages: 770-779
Description
「研究成果報告書概要(欧文)」より
Related Report
-
[Journal Article] A Elastolytic Cathepsin Induction/Activation System Exists in the Rat and Human Myocardium and is Upregulated in Hypertensive Heart Failure.2006
Author(s)
Cheng XW, Obata K, Kzuya M, Izawa H, Nakamura K, Asahi E, Saka M, Kimata T, Nagasaka T, Noda A, Nagata K, Jin H, Shi G P, Iguchi A, Murohara T, Yokota M
-
Journal Title
Hypertension 48
Pages: 979-987
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
[Journal Article] Pitavastatin improves cardiac function and survival in association with suppression of the myocardial endothelin system in a rat model of hypertensive heart failure.2006
Author(s)
Saka M, Obata K, Ichihara S, Cheng XW, Kimata H, Takao Nishizawa, Noda K, Izawa H, Nagata K, Murohara T, Yokota M.
-
Journal Title
Journal of Cardiovascular Pharmacology 47
Pages: 770-779
Related Report
-
[Journal Article] Effect of Green Tea Consumption on Endothelial Function and Circulating Endothelial Progenitor Cells in Chronic Smokers.2006
Author(s)
Kim W, Jeong MH, Cho SH, Yun HY, Chae HJ, Ahn YK, Lee MC, Cheng XW, Kondo T, Murohara T, Kang JC.
-
Journal Title
Circulation Journal 70
Pages: 1052-1057
NAID
Related Report
-
-
-
-
-
[Journal Article] Mechanisms of the Inhibitory Effect of Epigallocatechin-3-gallate on Cultured Human Vascular Smooth Muscle Cell Invasion2005
Author(s)
Cheng XW, Kuzuya M, Nakamura K, Di Qun, Liu Z, Hasegawa J, Iwata M, Murohara T, Yokota M, Iguchi A
-
Journal Title
Arteriosclerosis, Thrombosis, and Vascular Biology 25
Pages: 1864-1870
Description
「研究成果報告書概要(欧文)」より
Related Report
-