Diminazene aceturate, an angiotensin converting enzyme 2 (ACE2) activator, promotes cardioprotection in ischemia/reperfusion-induced cardiac injury

Peptides ◽  
2022 ◽  
pp. 170746
Author(s):  
Danielle C.O. Coutinho ◽  
Artur Santos-Miranda ◽  
Julliane V. Joviano-Santos ◽  
Giselle Foureaux ◽  
Anderson Santos ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Converting Enzyme ◽  
Diminazene Aceturate ◽  
Angiotensin Converting Enzyme 2

scholarly journals The Preventive Effects of Diminazene Aceturate in Renal Ischemia/Reperfusion Injury in Male and Female Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Maryam Malek ◽  
Mehdi Nematbakhsh
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Female Rats ◽  
Male Rats ◽  
Converting Enzyme ◽  
Diminazene Aceturate ◽  
Male And Female ◽  
Male And Female Rats

Background. Angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor (ACE2/Ang-1-7/MasR) appears to counteract most of the deleterious actions of angiotensin-converting enzyme/angiotensin II/angiotensin II receptor 1 (ACE/Ang II/AT1R) in renal ischemia/reperfusion (I/R) injury but ACE2 activity and its levels are sexually dimorphic in the kidney. This study was designed to evaluate the effects of activation endogenous ACE2 using the diminazene aceturate (DIZE) in renal I/R injury in male and female rats.Methods. 36 Wistar rats were divided into two groups of male and female and each group distinct to three subgroups (n=6). I/R group was subjected to 45 min of bilateral ischemia and 24 h of reperfusion, while treatment group received DIZE (15 mg/kg/day) for three days before the induction of I/R. The other group was assigned as the sham-operated group.Results. DIZE treatment in male rats caused a significant decrease in blood urea nitrogen (BUN), creatinine, liver functional indices, serum malondialdehyde (MDA), and increase kidney nitrite levels (P<0.05), and in female rats a significant increase in creatinine and decrease serum nitrite levels compared to the I/R group (P<0.05).Conclusions. DIZE may protect the male kidney from renal I/RI through antioxidant activity and elevation of circulating nitrite level.

scholarly journals Angiotensin-Converting Enzyme 2 (ACE2) Activator Diminazene Aceturate Ameliorates Endotoxin-Induced Uveitis in Mice

2014 ◽  
Vol 55 (6) ◽  
pp. 3809 ◽  
Author(s):  
Yiguo Qiu ◽  
Pollob Kumar Shil ◽  
Ping Zhu ◽  
Hongxia Yang ◽  
Amrisha Verma ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Diminazene Aceturate ◽  
Angiotensin Converting Enzyme 2

Anti-hypertensive Effects of Diminazene Aceturate: An Angiotensin- Converting Enzyme 2 Activator in Rats

2015 ◽  
Vol 23 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Marilda L.A. De Maria ◽  
Liliane D. Araújo ◽  
Rodrigo A. Fraga-Silva ◽  
Letícia A.S. Pereira ◽  
Heder J. Ribeiro ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Diminazene Aceturate ◽  
Angiotensin Converting Enzyme 2

scholarly journals Ocular Inserts for Sustained Release of the Angiotensin-Converting Enzyme 2 Activator, Diminazene Aceturate, to Treat Glaucoma in Rats

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0133149 ◽  
Author(s):  
Giselle Foureaux ◽  
Juçara Ribeiro Franca ◽  
José Carlos Nogueira ◽  
Gustavo de Oliveira Fulgêncio ◽  
Tatiana Gomes Ribeiro ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Sustained Release ◽  
Converting Enzyme ◽  
Diminazene Aceturate ◽  
Angiotensin Converting Enzyme 2

scholarly journals Diminazene Aceturate Enhances Angiotensin-Converting Enzyme 2 Activity and Attenuates Ischemia-Induced Cardiac Pathophysiology

Hypertension ◽  
2013 ◽  
Vol 62 (4) ◽  
pp. 746-752 ◽  
Author(s):  
YanFei Qi ◽  
Juan Zhang ◽  
Colleen T. Cole-Jeffrey ◽  
Vinayak Shenoy ◽  
Andrew Espejo ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Diminazene Aceturate ◽  
Angiotensin Converting Enzyme 2 ◽  
Cardiac Pathophysiology

Abstract TP102: Human Placental Mesenchymal Stem Cells Derived Exosome-Angiotensin Converting Enzyme-2 Dependent Protection in Ischemic Stroke Injury

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Mansoureh Barzegar ◽  
Yuping Wang ◽  
Jungmi W. Yun ◽  
Oleg Chernyshev ◽  
Roger Kelley ◽  
...  
Keyword(s):  
Stem Cells ◽  
Blood Flow ◽  
Mesenchymal Stem Cells ◽  
Ischemic Stroke ◽  
Angiotensin Converting Enzyme ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Placental Mesenchymal Stem Cells

Following thrombolytic therapy for stroke, ischemia/reperfusion (I/R) mediated inflammation often disrupts the blood brain barrier (BBB). This can enhance expression of endothelial adhesion markers and perturb normal blood flow regulation. Proposed benefits of stem cell therapy (SCT) in stroke, besides long-term trans-differentiation into neural cells, include secretion of protective factors, which partly depends on exosomes released by stem cells. We evaluated human placenta mesenchymal stem cells (hPMSC) as potential ameliorative SCT in an acute ischemic stroke model. We hypothesize that hPMSC would achieve site-specific suppression of post-ischemic immune cell transmigration, preservation of the BBB and maintenance of blood flow via ‘paracrine’ signaling pathways in acute stroke injury.We found that intraperitoneal (IP) administration of hPMSC at the time of reperfusion, using the middle cerebral artery occlusion (MCAO)/reperfusion model, produced significant protection ( p =0.0001) of the ipsilateral hemisphere. We also demonstrated that hPMSC-treated MCAO mice exhibited significantly greater neurological recovery ( p <0.0001) compared to untreated MCAO, an effect which was accompanied by significant restoration of blood flow ( p <0.01) to the MCAO-stressed brains. Using Evans Blue dye assay, we also observed significant ( p =0.004) improvement of BBB integrity in ipsilateral hemispheres of hPMSC-treated mice vs MCAO controls. Furthermore, we determined that hPMSC-derived exosomes contribute to paracrine based protection of hPMSC in MCAO model. Importantly, we found that hPMSC/exosome protection is mediated partly by the function of angiotensin converting enzyme 2 (ACE2). To evaluate the contribution of ACE2 in protection of the brain after ischemic stroke, we first demonstrated that hPMSC and their exosomes express ACE2. Second, mice injected with hPMSC which had been pre-treated with the specific ACE2 inhibitor (10μM) MLN-4760, showed tissue injury and neurological behavior similar to that seen in untreated MCAO.We conclude that pleiotropic factors associated with hPMSC administration can have a favorable impact on blood flow, BBB integrity potentially alleviating the detrimental effects of ischemic stroke.

scholarly journals SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes

2020 ◽  
Vol 116 (14) ◽  
pp. 2207-2215 ◽  
Author(s):  
Denisa Bojkova ◽  
Julian U G Wagner ◽  
Mariana Shumliakivska ◽  
Galip S Aslan ◽  
Umber Saleem ◽  
...  
Keyword(s):  
Stem Cell ◽  
Angiotensin Converting Enzyme ◽  
Pluripotent Stem Cell ◽  
Cardiac Injury ◽  
Induced Pluripotent Stem Cell ◽  
Viral Rna ◽  
Dependent Manner ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Induced Pluripotent

Abstract Aims Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has emerged as a global pandemic. SARS-CoV-2 infection can lead to elevated markers of cardiac injury associated with higher risk of mortality. It is unclear whether cardiac injury is caused by direct infection of cardiomyocytes or is mainly secondary to lung injury and inflammation. Here, we investigate whether cardiomyocytes are permissive for SARS-CoV-2 infection. Methods and results Two strains of SARS-CoV-2 infected human induced pluripotent stem cell-derived cardiomyocytes as demonstrated by detection of intracellular double-stranded viral RNA and viral spike glycoprotein expression. Increasing concentrations of viral RNA are detected in supernatants of infected cardiomyocytes, which induced infections in Caco-2 cell lines, documenting productive infections. SARS-CoV-2 infection and induced cytotoxic and proapoptotic effects associated with it abolished cardiomyocyte beating. RNA sequencing confirmed a transcriptional response to viral infection as demonstrated by the up-regulation of genes associated with pathways related to viral response and interferon signalling, apoptosis, and reactive oxygen stress. SARS-CoV-2 infection and cardiotoxicity was confirmed in a 3D cardiosphere tissue model. Importantly, viral spike protein and viral particles were detected in living human heart slices after infection with SARS-CoV-2. Coronavirus particles were further observed in cardiomyocytes of a patient with coronavirus disease 2019. Infection of induced pluripotent stem cell-derived cardiomyocytes was dependent on cathepsins and angiotensin-converting enzyme 2, and was blocked by remdesivir. Conclusion This study demonstrates that SARS-CoV-2 infects cardiomyocytes in vitro in an angiotensin-converting enzyme 2- and cathepsin-dependent manner. SARS-CoV-2 infection of cardiomyocytes is inhibited by the antiviral drug remdesivir.

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