Telmisartan acts through the modulation of ACE-2/ANG 1–7/mas receptor in rats with dilated cardiomyopathy induced by experimental autoimmune myocarditis

Sukumaran, Vijayakumar; Veeraveedu, Punniyakoti T.; Gurusamy, Narasimman; Lakshmanan, Arun Prasath; Yamaguchi, Kensei; Ma, Minghong; Suzuki, Kenji; Kodama, Makoto; Watanabe, Kenichi

doi:10.1016/j.lfs.2011.11.018

Cited by 53 publications

(47 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This systematic study of immunization protocols reveals that EAM can be reliably induced in rats with half the number of injections and 25% of the dose as compared to previously published protocols (Kodama et al 1990, Ishiyama et al 1998, Saito et al 2002, Sato et al 2002, Suzuki et al 2008, Korkusuz et al 2009, Arumugam et al 2012a,b, Hirano et al 2013, Song et al 2012, Sukumaran et al 2012. The optimized protocol reduces distress and mortality of the animals, preparation time and costs in EAM studies.…”

Section: Discussionmentioning

confidence: 77%

“…All protocols use Lewis rats, which are reported to be the only rat strain susceptible to EAM induction (Kodama et al 1990, Ishiyama et al 1998, Smith 2001, Saito et al 2002, Sato et al 2002, Suzuki et al 2008, Korkusuz et al 2009, Otsuka et al 2009, Arumugam et al 2012a,b, Hirano et al 2013, Kromen et al 2012, Song et al 2012, Sukumaran et al 2012. Some protocols describe a subcutaneous (SC) injection to the neck and flanks (Smith 2001, Otsuka et al 2009), but most protocols use the rear footpad (RF) immunization (Kodama et al 1990, Ishiyama et al 1998, Saito et al 2002, Sato et al 2002, Suzuki et al 2008, Korkusuz et al 2009, Arumugam et al 2012a,b, Hirano et al 2013, Song et al 2012, Sukumaran et al 2012. One of the most widely used protocols is based on a two-stage RF injection protocol (Kodama et al 1993, Maeda et al 2005.…”

mentioning

confidence: 99%

“…One of the most widely used protocols is based on a two-stage RF injection protocol (Kodama et al 1993, Maeda et al 2005. The dose of myosin and the corresponding injected volume also differ between protocols (Korkusuz et al 2009, Song et al 2012, Sukumaran et al 2012. The dose ranges from 0.5 mg to 1 mg myosin administered in the volume of 0.1 mL to as much as 0.5 mL of solution (Kodama et al 1990, Ishiyama et al 1998, Smith 2001, Saito et al 2002, Sato et al 2002, Suzuki et al 2008, Korkusuz et al 2009, Otsuka et al 2009, Arumugam et al 2012a,b, Hirano et al 2013, Kromen et al 2012, Song et al 2012, Sukumaran et al 2012.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Mortality and morbidity in different immunization protocols for experimental autoimmune myocarditis in rats

et al. 2014

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 77%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Mortality and morbidity in different immunization protocols for experimental autoimmune myocarditis in rats

et al. 2014

View full text Add to dashboard Cite

show abstract

“…ARBs increased the expressions of ACE2 and Ang-(1-7)/Mas; reduced the expression of inflammatory cytokines TNF-a, IFN-c, IL-1b, and IL-6; and increased the expression of anti-inflammatory cytokine IL-10 in an animal model of autoimmune myocarditis. 58,59 Therefore, ACE2 may be another feasible and more specific target in the protective RAS axis to delay the development of the common disease AMD.…”

Section: Ace2 Reduces Ab-induced Inflammation In Human Rpementioning

confidence: 99%

Overexpression of Angiotensin-Converting Enzyme 2 Ameliorates Amyloid β-Induced Inflammatory Response in Human Primary Retinal Pigment Epithelium

Lin

Qiu

et al. 2017

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Overexpression of angiotensin-converting enzyme 2 ameliorates amyloid b-induced inflammatory response in human primary retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2017;58:3018-3028. DOI:10.1167/ iovs.17-21546 PURPOSE. Amyloid-b (Ab) is a major constituent of drusen, which is a hallmark of early AMD. The purpose of this study was to investigate whether enhancement of ACE2, an important component of the protective angiotensin-converting enzyme 2 (ACE2)/Ang-(1-7)/Mas axis of the renin angiotensin system (RAS), ameliorates Ab-induced inflammatory response in human RPE cells. METHODS.Annexin-V FITC/propidium iodide assay for detecting apoptosis rate was used to determine the optimum concentration and incubation time of Ab1-42. ACE2 plasmid was transfected into primary cultured human RPE (hRPE) and ARPE-19 cells for 6 hours followed by stimulation with Ab1-42 at the concentration of 1 lM for 48 hours. Gene expression was detected by real-time PCR and protein levels were determined by Western blotting or ELISA. A779, an antagonist of Ang-(1-7), was used to further confirm the involvement of ACE2/Ang-(1-7)/Mas axis. RESULTS.Flow cytometry showed that the optimal concentration of Ab1-42 was 1 lM and the optimal incubation time was 48 hours. Ab1-42 upregulated the expression of IL-1b and monocyte chemoattractant protein-1. ACE2 plasmid significantly upregulated the expression of ACE2 and Ang-(1-7) in hRPE and ARPE-19 cells. Activation of ACE2 reduced the overproduction of inflammatory cytokines at both mRNA and protein levels in hRPE and ARPE-19 cells stimulated with Ab1-42. Furthermore, an antagonist of Ang-(1-7), A779 reversed the anti-inflammatory effect of ACE2.CONCLUSIONS. Overexpression of ACE2 ameliorates Ab-induced inflammatory response by activating the ACE2/Ang-(1-7)/Mas axis in human RPE cells. Our data suggest that ACE2/Ang-(1-7)/Mas axis may be a promising target for developing novel therapies for inflammation response in AMD.

show abstract

“…NF-kB, iNOS. In addition, ARBs enhance the anti-inflammatory cytokines (37,38). Ang 1-7 directly blunts the Ang IIinduced activation of pro-inflammatory signalling in kidney cells.…”

Section: Anti-inflammatory Actions Of Ang 1-7mentioning

confidence: 99%

Angiotensin-(1-7): A Novel Peptide to Treat Hypertension and Nephropathy in Diabetes?

Padda

Shi

et al. 2015

J Diabetes Metab

View full text Add to dashboard Cite

The renin-angiotensin system (RAS) plays a pivotal role in mammalian homeostasis physiology. The RAS can be delineated into a classical RAS (the pressor arm) including angiotensinogen (Agt), renin, angiotensin-converting enzyme (ACE), angiotensin II (Ang II) and angiotensin type 1 receptor (AT1R), and a counterbalancing novel RAS (the depressor arm) including Agt, renin, angiotensin-converting enzyme-2 (ACE-2), angiotensin-(1-7) (Ang 1-7) and Ang 1-7 receptor (or Mas receptor (MasR)). Hyperglycemia (diabetes) induces severe tissue oxidative stress, which stimulates the pressor arm of the renal RAS axis and leads to an increase in ACE/ACE-2 ratio, with excessive formation of Ang II. There is a growing body of evidence for beneficial effects of the depressor arm of RAS (ACE-2/Ang 1-7/MasR) axis in diabetes, hypertension and several other diseased conditions. Evidence from in vitro, in vivo and clinical studies reflects anti-oxidant, antifibrotic, and anti-inflammatory properties of Ang 1-7. Most of the currently available therapies only target suppression of the pressor arm of RAS with angiotensin receptor blockers (ARBs) and ACE inhibitors (ACEi). However, it is time to consider simultaneous activation of the depressor arm for more effective outcomes. This review summarizes the recent updates on the protective role of Ang 1-7 in hypertension and kidney injury in diabetes, as well as the possible underlying mechanism(s) of Ang 1-7 action, suggesting that the ACE-2/Ang 1-7/MasR axis can be developed as a therapeutic target for the treatment of diabetes-induced hypertension and renal damage.

show abstract

Telmisartan acts through the modulation of ACE-2/ANG 1–7/mas receptor in rats with dilated cardiomyopathy induced by experimental autoimmune myocarditis

Cited by 53 publications

References 55 publications

Mortality and morbidity in different immunization protocols for experimental autoimmune myocarditis in rats

Mortality and morbidity in different immunization protocols for experimental autoimmune myocarditis in rats

Overexpression of Angiotensin-Converting Enzyme 2 Ameliorates Amyloid β-Induced Inflammatory Response in Human Primary Retinal Pigment Epithelium

Angiotensin-(1-7): A Novel Peptide to Treat Hypertension and Nephropathy in Diabetes?

Contact Info

Product

Resources

About