The effects of different angiotensin II type 1 receptor blockers on the regulation of the ACE-AngII-AT1 and ACE2-Ang(1–7)-Mas axes in pressure overload-induced cardiac remodeling in male mice

Wang, Xingxu; Ye, Yong; Gong, Hui; Wu, Jian; Yuan, Jie; Wang, Shijun; Yin, Peng; Ding, Zhiwen; Kang, Le; Qiu, Jian; Zhang, Weijing; Li, Yang; Ge, Junbo; Zou, Yunzeng

doi:10.1016/j.yjmcc.2016.05.012

Cited by 138 publications

(107 citation statements)

References 48 publications

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“…Recently, Wang et al . observed that losartan effectively inhibits pressure overload-induced cardiac remodelling by up-regulating ACE2 expression and down-regulating ACE expression25. Taken together, the previous studies and our results indicate similar cardioprotection of PFD and losartan, which may be attributed to the effects on RAS axes by alteration of the ACE/ACE2 ratio.…”

Section: Discussionsupporting

confidence: 87%

Pirfenidone controls the feedback loop of the AT1R/p38 MAPK/renin-angiotensin system axis by regulating liver X receptor-α in myocardial infarction-induced cardiac fibrosis

Han

Kang

et al. 2017

Sci Rep

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Pirfenidone (PFD), an anti-fibrotic small molecule drug, is used to treat fibrotic diseases, but its effects on myocardial infarction (MI)-induced cardiac fibrosis are unknown. The aim of this study was to determine the effects of PFD on MI-induced cardiac fibrosis and the possible underlying mechanisms in rats. After establishment of the model, animals were administered PFD by gavage for 4 weeks. During the development of MI-induced cardiac fibrosis, we found activation of a positive feedback loop between the angiotensin II type 1 receptor (AT1R)/phospho-p38 mitogen-activated protein kinase (p38 MAPK) pathway and renin-angiotensin system (RAS), which was accompanied by down-regulation of liver X receptor-α (LXR-α) expression. PFD attenuated body weight, heart weight, left ventricular weight, left ventricular systolic pressure, and ±dp/dtmax changes induced by MI, which were associated with a reduction in cardiac fibrosis, infarct size, and hydroxyproline concentration. Moreover, PFD inhibited the AT1R/p38 MAPK pathway, corrected the RAS imbalance [decreased angiotensin-converting enzyme (ACE), angiotensin II, and angiotensin II type 1 receptor expression, but increased ACE2 and angiotensin (1-7) activity and Mas expression] and strongly enhanced heart LXR-α expression. These results indicate that the cardioprotective effects of PFD may be due, in large part, to controlling the feedback loop of the AT1R/p38 MAPK/RAS axis by activation of LXR-α.

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Section: Discussionsupporting

confidence: 87%

Pirfenidone controls the feedback loop of the AT1R/p38 MAPK/renin-angiotensin system axis by regulating liver X receptor-α in myocardial infarction-induced cardiac fibrosis

Han

Kang

et al. 2017

Sci Rep

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“…The mice were anesthetized with 1%–2% isoflurane, and the heart rates were stably maintained between 450 and 500 beats per min. After the B- and M-mode images were acquired, the left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured as previously described [45]. All measurements were performed by three experienced technicians who were blinded to the animal groups.…”

Section: Methodsmentioning

confidence: 99%

Alginate Oligosaccharide Prevents Acute Doxorubicin Cardiotoxicity by Suppressing Oxidative Stress and Endoplasmic Reticulum-Mediated Apoptosis

Guo

Shi

et al. 2016

Marine Drugs

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Doxorubicin (DOX) is a highly potent chemotherapeutic agent, but its usage is limited by dose-dependent cardiotoxicity. DOX-induced cardiotoxicity involves increased oxidative stress and activated endoplasmic reticulum-mediated apoptosis. Alginate oligosaccharide (AOS) is a non-immunogenic, non-toxic and biodegradable polymer, with anti-oxidative, anti-inflammatory and anti-endoplasmic reticulum stress properties. The present study examined whether AOS pretreatment could protect against acute DOX cardiotoxicity, and the underlying mechanisms focused on oxidative stress and endoplasmic reticulum-mediated apoptosis. We found that AOS pretreatment markedly increased the survival rate of mice insulted with DOX, improved DOX-induced cardiac dysfunction and attenuated DOX-induced myocardial apoptosis. AOS pretreatment mitigated DOX-induced cardiac oxidative stress, as shown by the decreased expressions of gp91 (phox) and 4-hydroxynonenal (4-HNE). Moreover, AOS pretreatment significantly decreased the expression of Caspase-12, C/EBP homologous protein (CHOP) (markers for endoplasmic reticulum-mediated apoptosis) and Bax (a downstream molecule of CHOP), while up-regulating the expression of anti-apoptotic protein Bcl-2. Taken together, these findings identify AOS as a potent compound that prevents acute DOX cardiotoxicity, at least in part, by suppression of oxidative stress and endoplasmic reticulum-mediated apoptosis.

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“…This turns out to be a very complex relationship and is currently still very controversial. On the one hand, it has been found that in animal models, ACE inhibitors [21] and ARBs can increase the expression of ACE2 receptors [22], which theoretically can increase the ability of SARS-CoV-2 to enter cells. However, the data on this is inconsistent, and may in fact be tissue dependent, dosage dependent and may vary among different ARBs [22,23].…”

Section: Regulation Network After Infectionmentioning

confidence: 99%

Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19

Zhang

et al. 2020

Journal of Autoimmunity

246

229

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It has been reported that SARS-CoV-2 may use ACE2 as a receptor to gain entry into human cells, in a way similar to that of SARS-CoV. Analyzing the distribution and expression level of ACE2 may therefore help reveal underlying mechanisms of viral susceptibility and post-infection modulation. In this study, we utilized previously uploaded information on ACE2 expression in various conditions including SARS-CoA to evaluate the role of ACE2 in SARS-CoV and extrapolate that to COVID-19. We found that the expression of ACE2 in healthy populations and patients with underlying diseases was not significantly different. However, based on the elevated expression of ACE2 in cigarette smokers, we speculate that long-term smoking may be a risk factor for COVID-19. Analysis of ACE2 in SARS-CoV infected cells suggests that ACE2 is not only a receptor but is also involved in post-infection regulation, including immune response, cytokine secretion, and viral genome replication. Moreover, we constructed Protein-protein interaction (PPI) networks and identified hub genes in viral activity and cytokine secretion. Our findings may help clinicians and researchers gain more insight into the pathogenesis of SARS-CoV-2 and design therapeutic strategies for COVID-19.

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The effects of different angiotensin II type 1 receptor blockers on the regulation of the ACE-AngII-AT1 and ACE2-Ang(1–7)-Mas axes in pressure overload-induced cardiac remodeling in male mice

Cited by 138 publications

References 48 publications

Pirfenidone controls the feedback loop of the AT1R/p38 MAPK/renin-angiotensin system axis by regulating liver X receptor-α in myocardial infarction-induced cardiac fibrosis

Pirfenidone controls the feedback loop of the AT1R/p38 MAPK/renin-angiotensin system axis by regulating liver X receptor-α in myocardial infarction-induced cardiac fibrosis

Alginate Oligosaccharide Prevents Acute Doxorubicin Cardiotoxicity by Suppressing Oxidative Stress and Endoplasmic Reticulum-Mediated Apoptosis

Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19

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