Is the cardioprotective effect of the ACE2 activator diminazene aceturate more potent than the ACE inhibitor enalapril on acute myocardial infarction in rats?

Badae, Noha Mohamed; Naggar, Asmaa Samy El; Sayed, Samiha Mahmoud El

doi:10.1139/cjpp-2019-0078

Cited by 14 publications

(7 citation statements)

References 54 publications

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“…This study also revealed increased Ang-(1–7), ACE2, and MasR, and decreased ACE and AT1R expression in the myocardium. Another study reported that the administration of DIZE for four weeks could significantly increase myocardial ACE2 protein concentration after the myocardial infarction, as well as improve cardiac function by preserving carotid flow, stroke volume, and cardiac output [ 20 ]. Taken together, these data support the role of DIZE in improving the function of Ang-(1–7)/MasR by activating ACE2 and elevating cardiac ACE2 protein to play a protective role in the pathogenesis of cardiovascular disorders.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown DIZE to have an antihypertensive effect, similar to that of ACE inhibitors [27,28]. In models of acute myocardial infarction and chronic heart failure, the administration of DIZE could reduce the size of the myocardial infarction and improve ventricular systolic and diastolic function, as well as inhibit myocardial fibrosis [14,20,24,[29][30][31]. The underlying protective mechanism of DIZE on the cardiovascular system is still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…DIZE (Cayman Chemical, Michigan, USA) was dissolved to a final concentration of 2 mg/mL in normal saline. The CLP + DIZE group was injected subcutaneously with the DIZE solution (15 mg/kg) 30 minutes prior to the operation [20], whereas the sham and CLP groups received 7.5 mL/kg normal saline injected subcutaneously.…”

Section: Study Protocolmentioning

confidence: 99%

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Diminazene aceturate mitigates cardiomyopathy by interfering with renin-angiotensin system in a septic rat model

Wang

et al. 2022

BMC Pharmacol Toxicol

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Background There were limited studies investigating treatments of septic cardiomyopathy (SCM), which is a common complication during sepsis. A septic rat model created by cecal ligation and puncture (CLP) was used to investigate the effects of diminazene aceturate (DIZE) in SCM. Methods A total of 151 Wistar rats were randomly assigned into the sham, CLP, or CLP + DIZE group. Data evaluated postoperatively at 6, 12, 24, and 48 hours included: cardiac function; plasma concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6, angiotensin-(1–7) [Ang-(1–7)], angiotensin II (AngII), troponin I, and brain natriuretic peptide; expression levels of myocardial Ang-(1–7), angiotensin-converting enzyme (ACE), ACE2, and angiotensin type 1 and Mas receptors; and histological changes. Results We found that the CLP + DIZE group had a lower mortality compared to the CLP group (38.5% versus 61.5%) within 48 h postoperatively, although without statistical significance. In contrast to the sham group, the CLP group had decreased cardiac functions, increased myocardial injuries, and higher TNF-α levels, which were ameliorated in the CLP + DIZE group. Furthermore, administration of DIZE could reverse the decreases of myocardial Ang-(1–7) and ACE2 expressions in the CLP group, which finally minimized the myocardial microstructure disruptions. Conclusions It was concluded that DIZE could mitigate the development of SCM and preserve cardiac function during sepsis possibly by interfering with the renin-angiotensin system through promoting myocardial ACE2 expression and restoring local Ang-(1–7) levels.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Diminazene aceturate mitigates cardiomyopathy by interfering with renin-angiotensin system in a septic rat model

Wang

et al. 2022

BMC Pharmacol Toxicol

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“…Treatment of ex vivo hearts by administration of 10 −8 M Ang(1-7) into the bath solution using Langendorff technique re-established the impulse conduction during ischemia-reperfusion and reduced incidence of arrhythmias during IR, possibly due to cardiomyocyte hyperpolarization via the activation of sodium pump [ 89 ]. Activation of ACE2 by diminazene aceturate (DIZE) treatment [ 86 , 90 , 91 , 92 ] led to an improvement of almost all evaluated parameters (however, lacking evidence against amelioration of hypertrophy). These effects were abolished by ACE2 inhibition (“compound 16”) [ 84 , 86 ] or by Mas-receptor antagonist (A779) [ 24 , 88 ].…”

Section: Ace2 Deficiency-related Pathologies Underlying Hypoxiamentioning

confidence: 99%

Alternative RAS in Various Hypoxic Conditions: From Myocardial Infarction to COVID-19

Rajtík

Galis

Bartosova

et al. 2021

IJMS

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Alternative branches of the classical renin–angiotensin–aldosterone system (RAS) represent an important cascade in which angiotensin 2 (AngII) undergoes cleavage via the action of the angiotensin-converting enzyme 2 (ACE2) with subsequent production of Ang(1-7) and other related metabolites eliciting its effects via Mas receptor activation. Generally, this branch of the RAS system is described as its non-canonical alternative arm with counterbalancing actions to the classical RAS, conveying vasodilation, anti-inflammatory, anti-remodeling and anti-proliferative effects. The implication of this branch was proposed for many different diseases, ranging from acute cardiovascular conditions, through chronic respiratory diseases to cancer, nonetheless, hypoxia is one of the most prominent common factors discussed in conjugation with the changes in the activity of alternative RAS branches. The aim of this review is to bring complex insights into the mechanisms behind the various forms of hypoxic insults on the activity of alternative RAS branches based on the different duration of stimuli and causes (acute vs. intermittent vs. chronic), localization and tissue (heart vs. vessels vs. lungs) and clinical relevance of studied phenomenon (experimental vs. clinical condition). Moreover, we provide novel insights into the future strategies utilizing the alternative RAS as a diagnostic tool as well as a promising pharmacological target in serious hypoxia-associated cardiovascular and cardiopulmonary diseases.

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“…12 Moreover, Entresto can also effectively inhibit the proliferation of vascular endothelial cells, smooth muscle cells and cardiomyocytes and suppress the aldosterone secretion, therefore alleviating the ventricular remodeling in AMI patients. [13][14][15][16][17] NT-proBNP is a long amino acid peptide chain secreted in case of heart failure, and it has been employed for the diagnosis of heart failure. 18 The significant increase or decrease of serum NT-proBNP level also predicts the elevated risk of sudden death and hospitalization.…”

mentioning

confidence: 99%

Effect of Emergency Percutaneous Coronary Intervention Combined with Sacubitril and Valsartan on the Cardiac Prognosis in Patients with Acute Myocardial Infarction

Fan¹,

Wang²,

Wang³

et al. 2023

IJGM

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Purpose This study aimed to investigate the effect of emergency percutaneous coronary intervention (PCI) combined with sacubitril-valsartan (Entresto) on the cardiac prognosis in patients with acute myocardial infarction (AMI). Patients and Methods A total of 78 AMI patients who were treated in our hospital between January 2020 and September 2021 were included and randomly divided into treatment group and control group (n=39 per group). In the control group, patients were treated with primary PCI combined with irbesartan; in the treatment group, patients were treated with primary PCI combined with Entresto; pharmacotherapy lasted for 3 months. The left ventricular remodeling indexes, serum N-terminal B-type natriuretic peptide precursor (NT-proBNP), serum homocysteine (HCY), cystatin C (CysC) and results of 6-minute walk test (6MWT) before and after treatment were compared between two groups. The incidence of major adverse cardiovascular events (MACE) was determined and compared between them. Results (1) Before treatment, there were no marked differences in the left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), interventricular septum thickness (IVST), NT-proBNP, left ventricular ejection fraction (LVEF), HCY, CysC, and results of 6MWT between two groups (P>0.05). After treatment, the LVEDS, LVEDD, NT-proBNP, HCY and CysC in the control group were significantly higher than in the treatment group (P<0.05). The recovery of LVEF and 6MWT in the treatment group was significantly better than in the control group (P<0.05). After treatment, there was no significant difference in the IVST between two groups (P>0.05). (2) The incidence of MACE in the control group was significantly higher than in the treatment group (P<0.05). Conclusion Compared with irbesartan, Entresto can further improve the cardiac function, prevent ventricular remodeling, and further optimize the clinical efficacy of PCI in AMI patients.

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Is the cardioprotective effect of the ACE2 activator diminazene aceturate more potent than the ACE inhibitor enalapril on acute myocardial infarction in rats?

Cited by 14 publications

References 54 publications

Diminazene aceturate mitigates cardiomyopathy by interfering with renin-angiotensin system in a septic rat model

Diminazene aceturate mitigates cardiomyopathy by interfering with renin-angiotensin system in a septic rat model

Alternative RAS in Various Hypoxic Conditions: From Myocardial Infarction to COVID-19

Effect of Emergency Percutaneous Coronary Intervention Combined with Sacubitril and Valsartan on the Cardiac Prognosis in Patients with Acute Myocardial Infarction

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