Tags

Type your tag names separated by a space and hit enter

Azilsartan ameliorates diabetic cardiomyopathy in young db/db mice through the modulation of ACE-2/ANG 1-7/Mas receptor cascade.
Biochem Pharmacol. 2017 11 15; 144:90-99.BP

Abstract

Hyperglycemia up-regulates intracellular angiotensin II (ANG-II) production in cardiac myocytes. This study investigated the hemodynamic and metabolic effects of azilsartan (AZL) treatment in a mouse model of diabetic cardiomyopathy and whether the cardioprotective effects of AZL are mediated by the angiotensin converting enzyme (ACE)-2/ANG 1-7/Mas receptor (R) cascade. Control db/+ and db/db mice (n=5 per group) were treated with vehicle or AZL (1 or 3mg/kg/d oral gavage) from the age of 8 to 16weeks. Echocardiography was then performed and myocardial protein levels of ACE-2, Mas R, AT1R, AT2R, osteopontin, connective tissue growth factor (CTGF), atrial natriuretic peptide (ANP) and nitrotyrosine were measured by Western blotting. Oxidative DNA damage and inflammatory markers were assessed by immunofluorescence of 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor (TNF)-α and interleukin 6 (IL-6). Compared with db/+ mice, the vehicle-treated db/db mice developed obesity, hyperglycemia, hyperinsulinemia and diastolic dysfunction along with cardiac hypertrophy and fibrosis. AZL treatment lowered blood pressure, fasting blood glucose and reduced peak plasma glucose during an oral glucose tolerance test. AZL-3 treatment resulted in a significant decrease in the expression of cytokines, oxidative DNA damage and cardiac dysfunction. Moreover, AZL-3 treatment significantly abrogated the downregulation of ACE-2 and Mas R protein levels in db/db mice. Furthermore, AZL treatment significantly reduced cardiac fibrosis, hypertrophy and their marker molecules (osteopontin, CTGF, TGF-β1 and ANP). Short-term treatment with AZL-3 reversed abnormal cardiac structural remodeling and partially improved glucose metabolism in db/db mice by modulating the ACE-2/ANG 1-7/Mas R pathway.

Authors+Show Affiliations

Department of Artificial Organs, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan; Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan. Electronic address: svkumar1979@ncvc.go.jp.Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan.Department of Artificial Organs, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan.Department of Advanced Medical Research for Pulmonary Hypertension, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan.Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan; Department of Physiology and Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, Australia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28789938

Citation

Sukumaran, Vijayakumar, et al. "Azilsartan Ameliorates Diabetic Cardiomyopathy in Young Db/db Mice Through the Modulation of ACE-2/ANG 1-7/Mas Receptor Cascade." Biochemical Pharmacology, vol. 144, 2017, pp. 90-99.
Sukumaran V, Tsuchimochi H, Tatsumi E, et al. Azilsartan ameliorates diabetic cardiomyopathy in young db/db mice through the modulation of ACE-2/ANG 1-7/Mas receptor cascade. Biochem Pharmacol. 2017;144:90-99.
Sukumaran, V., Tsuchimochi, H., Tatsumi, E., Shirai, M., & Pearson, J. T. (2017). Azilsartan ameliorates diabetic cardiomyopathy in young db/db mice through the modulation of ACE-2/ANG 1-7/Mas receptor cascade. Biochemical Pharmacology, 144, 90-99. https://doi.org/10.1016/j.bcp.2017.07.022
Sukumaran V, et al. Azilsartan Ameliorates Diabetic Cardiomyopathy in Young Db/db Mice Through the Modulation of ACE-2/ANG 1-7/Mas Receptor Cascade. Biochem Pharmacol. 2017 11 15;144:90-99. PubMed PMID: 28789938.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Azilsartan ameliorates diabetic cardiomyopathy in young db/db mice through the modulation of ACE-2/ANG 1-7/Mas receptor cascade. AU - Sukumaran,Vijayakumar, AU - Tsuchimochi,Hirotsugu, AU - Tatsumi,Eisuke, AU - Shirai,Mikiyasu, AU - Pearson,James T, Y1 - 2017/08/05/ PY - 2017/05/02/received PY - 2017/07/28/accepted PY - 2017/8/10/pubmed PY - 2017/10/20/medline PY - 2017/8/10/entrez KW - Angiotensin-II KW - Azilsartan KW - Azilsartan Pubmed CID: 9825285 KW - Fibrosis KW - Hypertrophy KW - Inflammation KW - Oxidative stress SP - 90 EP - 99 JF - Biochemical pharmacology JO - Biochem Pharmacol VL - 144 N2 - Hyperglycemia up-regulates intracellular angiotensin II (ANG-II) production in cardiac myocytes. This study investigated the hemodynamic and metabolic effects of azilsartan (AZL) treatment in a mouse model of diabetic cardiomyopathy and whether the cardioprotective effects of AZL are mediated by the angiotensin converting enzyme (ACE)-2/ANG 1-7/Mas receptor (R) cascade. Control db/+ and db/db mice (n=5 per group) were treated with vehicle or AZL (1 or 3mg/kg/d oral gavage) from the age of 8 to 16weeks. Echocardiography was then performed and myocardial protein levels of ACE-2, Mas R, AT1R, AT2R, osteopontin, connective tissue growth factor (CTGF), atrial natriuretic peptide (ANP) and nitrotyrosine were measured by Western blotting. Oxidative DNA damage and inflammatory markers were assessed by immunofluorescence of 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor (TNF)-α and interleukin 6 (IL-6). Compared with db/+ mice, the vehicle-treated db/db mice developed obesity, hyperglycemia, hyperinsulinemia and diastolic dysfunction along with cardiac hypertrophy and fibrosis. AZL treatment lowered blood pressure, fasting blood glucose and reduced peak plasma glucose during an oral glucose tolerance test. AZL-3 treatment resulted in a significant decrease in the expression of cytokines, oxidative DNA damage and cardiac dysfunction. Moreover, AZL-3 treatment significantly abrogated the downregulation of ACE-2 and Mas R protein levels in db/db mice. Furthermore, AZL treatment significantly reduced cardiac fibrosis, hypertrophy and their marker molecules (osteopontin, CTGF, TGF-β1 and ANP). Short-term treatment with AZL-3 reversed abnormal cardiac structural remodeling and partially improved glucose metabolism in db/db mice by modulating the ACE-2/ANG 1-7/Mas R pathway. SN - 1873-2968 UR - https://www.unboundmedicine.com/medline/citation/28789938/Azilsartan_ameliorates_diabetic_cardiomyopathy_in_young_db/db_mice_through_the_modulation_of_ACE_2/ANG_1_7/Mas_receptor_cascade_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(17)30510-5 DB - PRIME DP - Unbound Medicine ER -