Monoamine oxidase is a source of cardiac oxidative stress in obese rats: the beneficial role of metformin

Merce, Adrian P.; Ionică, Loredana Nicoleta; Bînă, Anca M.; Popescu, Simona; Lighezan, Rodica; Petrescu, Lucian; Borza, Claudia; Sturza, Adrian; Muntean, Danina; Creţu, Octavian

doi:10.1007/s11010-022-04490-5

Cited by 15 publications

(10 citation statements)

References 49 publications

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“…We also demonstrated here that Metf is able to mitigate the oxidative stress, in particular the H2O2 generation. Important, in a previous study we reported that metformin does not have ROS scavenger properties (31), thus the reduction of ROS is the consequence of direct effect on ROS generation and/or on the antioxidant capacity, hypotheses that will be addressed in future studies.…”

Section: Discussionmentioning

confidence: 95%

Metformin Reverses the Effects of Angiotensin 2 in Human Mammary Arteries by Modulating the Expression of Nitric Oxide Synthases

Merce

Buriman

Lascu³

et al. 2022

Serbian Journal of Experimental and Clinical Research

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Angiotensin 2 impairs vascular function by activation of reactive oxygen species (ROS) production and development of endothelial dysfunction. Metformin, the first-line therapeutic agent for type 2 diabetes mellitus, has vascular protective properties, beyond its glucose lowering effects. The aim of the present study was to in-vestigate the interaction between metformin and angiotensin 2 in human internal mammary arteries harvested from patients with coronary heart disease undergoing revascularization procedure, by evaluation of vascular function, reactive oxygen species (ROS) production and the gene expression of nitric oxide (NO) synthases (endothelial – eNOS, neuronal – nNOS and inducible – iNOS). To this aim, vascular samples were incubated with angiotensin 2 (Ang2, 12 h) with/without metformin (Metf, 10 μM) and used for ROS measurement (FOX assay), vascular reactivity in organ bath (contractility to phenylephrine, relaxation to acetylcholine, con-tractility to NG-nitro-L-arginine methyl ester/L-NAME) and RT-PCT studies. Acute incubation of the vascular rings with Ang2 im-paired vascular reactivity (increase contractility, decrease relax-ation), increased ROS production, supressed eNOS/nNOS and in-creased iNOS mRNA expression. Ex vivo incubation with metfor-min at a clinically relevant concentration reversed all these ef-fects. These data suggest that Metformin might be useful in allevi-ating endothelial dysfunction by improving the endothelial-de-pendent relaxation and mitigating oxidative stress in clinical set-ting associated with cardiovascular disease regardless the pres-ence of impaired glucose metabolism.

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Section: Discussionmentioning

confidence: 95%

Metformin Reverses the Effects of Angiotensin 2 in Human Mammary Arteries by Modulating the Expression of Nitric Oxide Synthases

Merce

Buriman

Lascu³

et al. 2022

Serbian Journal of Experimental and Clinical Research

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“…MAO‐A preferentially oxidizes serotonin, NE, and epinephrine, and MAO‐B preferentially oxidizes phenylethylamine and benzylamine [46]. A previous study showed that a high‐calorie junk‐food diet elicited increased expression of both MAO‐A and MAO‐B [47]. Meanwhile, a higher level of H 2 O 2 was found in obese heart tissue, and in vitro , MAO‐A or ‐B inhibitors could decrease the level of H 2 O 2 in ventricular cells [47].…”

Section: Discussionmentioning

confidence: 99%

“…A previous study showed that a high‐calorie junk‐food diet elicited increased expression of both MAO‐A and MAO‐B [47]. Meanwhile, a higher level of H 2 O 2 was found in obese heart tissue, and in vitro , MAO‐A or ‐B inhibitors could decrease the level of H 2 O 2 in ventricular cells [47]. Thus, we conjectured that MAO‐B may also contribute to the effects, which is similar to MAO‐A in obese rats.…”

Section: Discussionmentioning

confidence: 99%

Carotid baroreceptor stimulation prevents oxidative stress by inhibiting MAO‐A and prevents cardiac remodeling in obese rats

Dai

et al. 2023

Obesity

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Objective Sympathetic nervous system overactivation and abnormal lipid metabolism are featured in obesity and may lead to cardiac remodeling. The effects of carotid baroreceptor stimulation (CBS) on cardiac remodeling in obese rats and the underlying mechanisms were explored. Methods An obesity model was induced by 16‐week high‐fat diet feeding. A CBS device was implanted at the 8th week. Body weight and blood pressure measurements, electrocardiography, echocardiography, and glucose and insulin tolerance tests were conducted before sampling. Plasma analysis and histological and biological analyses of left ventricle were also performed. Neonatal rat cardiomyocytes cocultured with 3T3‐L1 in transwell chambers were used to investigate the mechanisms. Results CBS alleviated several manifestations of obesity, including increased body weight, high blood pressure, hyperlipidemia, and enhanced sympathetic activity. In obese hearts, norepinephrine levels decreased, and the monoamine oxidase A (MAO‐A) and reactive oxygen species level increased; these changes, as well as cardiac fibrosis, lipid metabolic disorders, and heart dysfunction, were inhibited by CBS. Neonatal rat cardiomyocytes incubated with norepinephrine showed MAO‐A upregulation, increased reactive oxygen species levels, lipid metabolic disorders, and inflammatory response, which were inhibited by clorgyline, a selective MAO‐A inhibitor. Conclusions CBS effectively suppresses sympathetic nervous system activity and oxidative stress mediated by MAO‐A and prevents cardiac remodeling in obese rats.

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“…[ 305 ]. While the inhibition of complex I of ETS has been the unequivocally demonstrated as therapeutic effect and lactic acidosis as toxic one, recent work has reported the ability of metformin (applied ex vivo in a therapeutic relevant concentration, 10 microM) to decrease the expression of monoamine oxidase (MAO, an enzyme at the outer mitochondrial membrane) and the related oxidative stress in both ventricular [ 306 ] and aortic [ 307 ] murine samples.…”

Section: Mitochondrial Effects Of the Main Classes Of Drugs Used In C...mentioning

confidence: 99%

Mitochondrial Effects of Common Cardiovascular Medications: The Good, the Bad and the Mixed

Bețiu

Noveanu

Hâncu

et al. 2022

IJMS

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Mitochondria are central organelles in the homeostasis of the cardiovascular system via the integration of several physiological processes, such as ATP generation via oxidative phosphorylation, synthesis/exchange of metabolites, calcium sequestration, reactive oxygen species (ROS) production/buffering and control of cellular survival/death. Mitochondrial impairment has been widely recognized as a central pathomechanism of almost all cardiovascular diseases, rendering these organelles important therapeutic targets. Mitochondrial dysfunction has been reported to occur in the setting of drug-induced toxicity in several tissues and organs, including the heart. Members of the drug classes currently used in the therapeutics of cardiovascular pathologies have been reported to both support and undermine mitochondrial function. For the latter case, mitochondrial toxicity is the consequence of drug interference (direct or off-target effects) with mitochondrial respiration/energy conversion, DNA replication, ROS production and detoxification, cell death signaling and mitochondrial dynamics. The present narrative review aims to summarize the beneficial and deleterious mitochondrial effects of common cardiovascular medications as described in various experimental models and identify those for which evidence for both types of effects is available in the literature.

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Monoamine oxidase is a source of cardiac oxidative stress in obese rats: the beneficial role of metformin

Cited by 15 publications

References 49 publications

Metformin Reverses the Effects of Angiotensin 2 in Human Mammary Arteries by Modulating the Expression of Nitric Oxide Synthases

Metformin Reverses the Effects of Angiotensin 2 in Human Mammary Arteries by Modulating the Expression of Nitric Oxide Synthases

Carotid baroreceptor stimulation prevents oxidative stress by inhibiting MAO‐A and prevents cardiac remodeling in obese rats

Mitochondrial Effects of Common Cardiovascular Medications: The Good, the Bad and the Mixed

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