Cardioprotective effects of telmisartan against heart failure in rats in-duced by experimental autoimmune myocarditis through the modulation of Angiotensin-Converting Enzyme-2/Angiotensin 1-7/Mas Receptor axis

Vijayakumar Sukumaran, Punniyakoti T. Veeraveedu, Narasimman Gurusamy, Ken'ichi Yamaguchi, Arun Lakshmanan, Meilei Ma, Kenji Suzuki, Makoto Kodama, Kenichi Watanabe

Research output: Contribution to journalArticle

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Abstract

Angiotensin-converting enzyme-2 (ACE-2) is a homolog of ACE that preferentially forms angiotensin-(ANG)-1-7 from angiotensin II (ANG II). We investigated the cardioprotective effects of telmisartan, a well-known angiotensin receptor blockers (ARBs) against experi-mental autoimmune myocarditis (EAM). EAM was induced in Lewis rats by immunization with porcine cardiac myosin. The rats were divided into two groups and treated with telmisartan (10 mg/kg/day) or vehicle for 21 days. Myocardial functional parameters were significantly improved by treatment with telmisartan compared with vehicle-treated rats. Telmisartan lowered myocardial protein expressions of NADPH oxidase subunits 3-nitrotyrosine, p47phox, p67 phox, Nox-4 and superoxide production significantly than vehicle-treated rats. In contrast myocardial protein levels of ACE-2, ANG 1-7 mas receptor were upregulated in the telmisartan treated group compared with those of vehicle-treated rats. The myocardial protein expression levels of tumor necrosis factor receptor (TNFR)-associated factor (TRAF)-2, C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP) 78 were decreased in the telmisartan treated rats compared with those of vehicle-treated rats. In addition, telmisartan treatment significantly decreased the protein expression levels of phospho-p38 mitogen-activated protein kinase (MAPK), phospho-JNK, phospho-ERK and phospho (MAPK) activated protein kinase-2 than with those of vehicle-treated rats. Moreover, telmisartan significantly decreased the production of proinflammatory cytokines, myocardial apoptotic markers and caspase-3 positive cells compared with those of vehicle-treated rats. Therefore, we suggest that telmisartan was beneficial protection against heart failure in rats, at least in part by suppressing inflammation, oxidative stress, ER stress as well as signaling pathways through the modulation of ACE2/ANG1-7/Mas receptor axis.

Original languageEnglish
Pages (from-to)1077-1092
Number of pages16
JournalInternational Journal of Biological Sciences
Volume7
Issue number7
Publication statusPublished - 19 Sep 2011
Externally publishedYes

Fingerprint

cardioprotective effect
angiotensins
myocarditis
peptidyl-dipeptidase A
Myocarditis
heart failure
Heart Failure
enzyme
receptors
protein
rats
mitogen-activated protein kinase
protein synthesis
Proteins
Transcription Factor CHOP
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
telmisartan
angiotensin converting enzyme 2
angiotensin I (1-7)
effect

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology

Cite this

Cardioprotective effects of telmisartan against heart failure in rats in-duced by experimental autoimmune myocarditis through the modulation of Angiotensin-Converting Enzyme-2/Angiotensin 1-7/Mas Receptor axis. / Sukumaran, Vijayakumar; Veeraveedu, Punniyakoti T.; Gurusamy, Narasimman; Yamaguchi, Ken'ichi; Lakshmanan, Arun; Ma, Meilei; Suzuki, Kenji; Kodama, Makoto; Watanabe, Kenichi.

In: International Journal of Biological Sciences, Vol. 7, No. 7, 19.09.2011, p. 1077-1092.

Research output: Contribution to journalArticle

Sukumaran, Vijayakumar ; Veeraveedu, Punniyakoti T. ; Gurusamy, Narasimman ; Yamaguchi, Ken'ichi ; Lakshmanan, Arun ; Ma, Meilei ; Suzuki, Kenji ; Kodama, Makoto ; Watanabe, Kenichi. / Cardioprotective effects of telmisartan against heart failure in rats in-duced by experimental autoimmune myocarditis through the modulation of Angiotensin-Converting Enzyme-2/Angiotensin 1-7/Mas Receptor axis. In: International Journal of Biological Sciences. 2011 ; Vol. 7, No. 7. pp. 1077-1092.
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abstract = "Angiotensin-converting enzyme-2 (ACE-2) is a homolog of ACE that preferentially forms angiotensin-(ANG)-1-7 from angiotensin II (ANG II). We investigated the cardioprotective effects of telmisartan, a well-known angiotensin receptor blockers (ARBs) against experi-mental autoimmune myocarditis (EAM). EAM was induced in Lewis rats by immunization with porcine cardiac myosin. The rats were divided into two groups and treated with telmisartan (10 mg/kg/day) or vehicle for 21 days. Myocardial functional parameters were significantly improved by treatment with telmisartan compared with vehicle-treated rats. Telmisartan lowered myocardial protein expressions of NADPH oxidase subunits 3-nitrotyrosine, p47phox, p67 phox, Nox-4 and superoxide production significantly than vehicle-treated rats. In contrast myocardial protein levels of ACE-2, ANG 1-7 mas receptor were upregulated in the telmisartan treated group compared with those of vehicle-treated rats. The myocardial protein expression levels of tumor necrosis factor receptor (TNFR)-associated factor (TRAF)-2, C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP) 78 were decreased in the telmisartan treated rats compared with those of vehicle-treated rats. In addition, telmisartan treatment significantly decreased the protein expression levels of phospho-p38 mitogen-activated protein kinase (MAPK), phospho-JNK, phospho-ERK and phospho (MAPK) activated protein kinase-2 than with those of vehicle-treated rats. Moreover, telmisartan significantly decreased the production of proinflammatory cytokines, myocardial apoptotic markers and caspase-3 positive cells compared with those of vehicle-treated rats. Therefore, we suggest that telmisartan was beneficial protection against heart failure in rats, at least in part by suppressing inflammation, oxidative stress, ER stress as well as signaling pathways through the modulation of ACE2/ANG1-7/Mas receptor axis.",
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AU - Gurusamy, Narasimman

AU - Yamaguchi, Ken'ichi

AU - Lakshmanan, Arun

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