Tags

Type your tag names separated by a space and hit enter

Superoxide-dependent cathepsin activation is associated with hypertensive myocardial remodeling and represents a target for angiotensin II type 1 receptor blocker treatment.
Am J Pathol. 2008 Aug; 173(2):358-69.AJ

Abstract

The elastolytic activity of cathepsins in the myocardium is implicated in hypertensive heart failure (HF). Given that reactive oxygen species are also implicated in protease activation associated with cardiac remodeling, we examined the role of the reactive oxygen species-induced cathepsin activation system in cardiac remodeling during the development of hypertensive HF. Dahl salt-sensitive hypertensive rats maintained on a high-salt diet were treated with vehicle, the cathepsin inhibitor E64d, or the angiotensin receptor blocker olmesartan from 12 to 19 weeks of age. Cathepsin expression and activity were increased in the left ventricle of HF rats; olmesartan inhibited these effects, restored the balance between elastin and collagen in the left ventricle, and suppressed degradation of the elastic lamina of coronary arteries of HF rats. Furthermore, olmesartan inhibited up-regulation of NADPH oxidase subunits and activity as well as superoxide generation. These effects of olmesartan were mimicked by E64d and were accompanied by amelioration of cardiac fibrosis. Finally, olmesartan and apocynin reduced angiotensin II-induced increases in cathepsin mRNA and protein levels in cultured rat neonatal cardiac myocytes. These data suggest that cathepsins likely trigger and promote cardiac remodeling and that blocking the angiotensin II type 1 receptor attenuates cathepsin expression and activity by inhibiting the production of superoxide by NADPH oxidase, thereby attenuating cardiac remodeling and dysfunction.

Authors+Show Affiliations

Department of Cardiovascular Research Medicine, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan. xianwu@med.nagoya-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18583318

Citation

Cheng, Xian Wu, et al. "Superoxide-dependent Cathepsin Activation Is Associated With Hypertensive Myocardial Remodeling and Represents a Target for Angiotensin II Type 1 Receptor Blocker Treatment." The American Journal of Pathology, vol. 173, no. 2, 2008, pp. 358-69.
Cheng XW, Murohara T, Kuzuya M, et al. Superoxide-dependent cathepsin activation is associated with hypertensive myocardial remodeling and represents a target for angiotensin II type 1 receptor blocker treatment. Am J Pathol. 2008;173(2):358-69.
Cheng, X. W., Murohara, T., Kuzuya, M., Izawa, H., Sasaki, T., Obata, K., Nagata, K., Nishizawa, T., Kobayashi, M., Yamada, T., Kim, W., Sato, K., Shi, G. P., Okumura, K., & Yokota, M. (2008). Superoxide-dependent cathepsin activation is associated with hypertensive myocardial remodeling and represents a target for angiotensin II type 1 receptor blocker treatment. The American Journal of Pathology, 173(2), 358-69. https://doi.org/10.2353/ajpath.2008.071126
Cheng XW, et al. Superoxide-dependent Cathepsin Activation Is Associated With Hypertensive Myocardial Remodeling and Represents a Target for Angiotensin II Type 1 Receptor Blocker Treatment. Am J Pathol. 2008;173(2):358-69. PubMed PMID: 18583318.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Superoxide-dependent cathepsin activation is associated with hypertensive myocardial remodeling and represents a target for angiotensin II type 1 receptor blocker treatment. AU - Cheng,Xian Wu, AU - Murohara,Toyoaki, AU - Kuzuya,Masafumi, AU - Izawa,Hideo, AU - Sasaki,Takeshi, AU - Obata,Koji, AU - Nagata,Kohzo, AU - Nishizawa,Takao, AU - Kobayashi,Masakazu, AU - Yamada,Takashi, AU - Kim,Weon, AU - Sato,Kohji, AU - Shi,Guo-Ping, AU - Okumura,Kenji, AU - Yokota,Mitsuhiro, Y1 - 2008/06/26/ PY - 2008/6/28/pubmed PY - 2008/9/25/medline PY - 2008/6/28/entrez SP - 358 EP - 69 JF - The American journal of pathology JO - Am. J. Pathol. VL - 173 IS - 2 N2 - The elastolytic activity of cathepsins in the myocardium is implicated in hypertensive heart failure (HF). Given that reactive oxygen species are also implicated in protease activation associated with cardiac remodeling, we examined the role of the reactive oxygen species-induced cathepsin activation system in cardiac remodeling during the development of hypertensive HF. Dahl salt-sensitive hypertensive rats maintained on a high-salt diet were treated with vehicle, the cathepsin inhibitor E64d, or the angiotensin receptor blocker olmesartan from 12 to 19 weeks of age. Cathepsin expression and activity were increased in the left ventricle of HF rats; olmesartan inhibited these effects, restored the balance between elastin and collagen in the left ventricle, and suppressed degradation of the elastic lamina of coronary arteries of HF rats. Furthermore, olmesartan inhibited up-regulation of NADPH oxidase subunits and activity as well as superoxide generation. These effects of olmesartan were mimicked by E64d and were accompanied by amelioration of cardiac fibrosis. Finally, olmesartan and apocynin reduced angiotensin II-induced increases in cathepsin mRNA and protein levels in cultured rat neonatal cardiac myocytes. These data suggest that cathepsins likely trigger and promote cardiac remodeling and that blocking the angiotensin II type 1 receptor attenuates cathepsin expression and activity by inhibiting the production of superoxide by NADPH oxidase, thereby attenuating cardiac remodeling and dysfunction. SN - 1525-2191 UR - https://www.unboundmedicine.com/medline/citation/18583318/Superoxide_dependent_cathepsin_activation_is_associated_with_hypertensive_myocardial_remodeling_and_represents_a_target_for_angiotensin_II_type_1_receptor_blocker_treatment_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(10)61613-6 DB - PRIME DP - Unbound Medicine ER -