Glycolaldehyde-Derived High-Molecular-Weight Advanced Glycation End-Products Induce Cardiac Dysfunction through Structural and Functional Remodeling of Cardiomyocytes

Deluyker, Dorien; Evens, L; Haesen, Sibren; Driesen, Ronald B.; Kuster, Diederik W.D.; Verboven, Maxim; Beliën, Hanne; Velden, Jolanda van der; Lambrichts, Ivo; Bito, Virginie

doi:10.33594/000000271

Cited by 6 publications

(6 citation statements)

References 49 publications

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“…Indeed, the activation of RAGEs stimulates the signaling of nuclear factor kappa B (NF-κB)-dependent proinflammatory mediators including tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, IL-6, and RAGE itself, initiating a vicious cycle [ 55 ]. What is more, the injection of high-molecular-weight (HMW-)AGEs induces cardiac dysfunction in vivo [ 56 ]. The hearts of the rats treated with HMW-AGEs were characterized by elevated mass as well as decreased contractility [ 56 ].…”

Section: Diabetic Cardiomyopathy (Dcm)mentioning

confidence: 99%

“…What is more, the injection of high-molecular-weight (HMW-)AGEs induces cardiac dysfunction in vivo [ 56 ]. The hearts of the rats treated with HMW-AGEs were characterized by elevated mass as well as decreased contractility [ 56 ]. The microscope analysis revealed cardiomyocytes’ concentric hypertrophy, whereas ultrastructural examination has shown disrupted cellular architecture, decreased mitochondrial density, and functionality [ 56 ].…”

Section: Diabetic Cardiomyopathy (Dcm)mentioning

confidence: 99%

“…The hearts of the rats treated with HMW-AGEs were characterized by elevated mass as well as decreased contractility [ 56 ]. The microscope analysis revealed cardiomyocytes’ concentric hypertrophy, whereas ultrastructural examination has shown disrupted cellular architecture, decreased mitochondrial density, and functionality [ 56 ]. What is more, other intracellular alterations due to HMW-AGEs’ injection such as disrupted Ca 2+ cycling and decreased myofilament function were described [ 56 ].…”

Section: Diabetic Cardiomyopathy (Dcm)mentioning

confidence: 99%

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Extracellular Vesicles in Diabetic Cardiomyopathy—State of the Art and Future Perspectives

Zygmunciak,

Stróżna,

Błażowska

et al. 2024

IJMS

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Cardiovascular complications are the most deadly and cost-driving effects of diabetes mellitus (DM). One of them, which is steadily attracting attention among scientists, is diabetes-induced heart failure, also known as diabetic cardiomyopathy (DCM). Despite significant progress in the research concerning the disease, a universally accepted definition is still lacking. The pathophysiology of the processes accelerating heart insufficiency in diabetic patients on molecular and cellular levels also remains elusive. However, the recent interest concerning extracellular vesicles (EVs) has brought promise to further clarifying the pathological events that lead to DCM. In this review, we sum up recent investigations on the involvement of EVs in DCM and show their therapeutic and indicatory potential.

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Section: Diabetic Cardiomyopathy (Dcm)mentioning

confidence: 99%

Section: Diabetic Cardiomyopathy (Dcm)mentioning

confidence: 99%

Section: Diabetic Cardiomyopathy (Dcm)mentioning

confidence: 99%

See 1 more Smart Citation

Extracellular Vesicles in Diabetic Cardiomyopathy—State of the Art and Future Perspectives

Zygmunciak,

Stróżna,

Błażowska

et al. 2024

IJMS

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“…and euthanized by injection with an overdose of sodium pentobarbital (Dolethal, Vetoquinol, 200 mg/kg, i.p.). Hearts were harvested and single cardiomyocytes were isolated from the LV by enzymatic dissociation through retrograde perfusion of the aorta, as described previously [58,59]. The hearts were perfused for 1 min with a normal Tyrode solution and then connected to a Langendorff perfusion system for following perfusion steps at 37 • C and 100% O 2 oxygenation.…”

Section: Cardiomyocyte Isolation and Unloaded Cell Shorteningmentioning

confidence: 99%

Combinational Therapy of Cardiac Atrial Appendage Stem Cells and Pyridoxamine: The Road to Cardiac Repair?

Evens

Beliën

D'Haese

et al. 2021

IJMS

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Myocardial infarction (MI) occurs when the coronary blood supply is interrupted. As a consequence, cardiomyocytes are irreversibly damaged and lost. Unfortunately, current therapies for MI are unable to prevent progression towards heart failure. As the renewal rate of cardiomyocytes is minimal, the optimal treatment should achieve effective cardiac regeneration, possibly with stem cells transplantation. In that context, our research group identified the cardiac atrial appendage stem cells (CASCs) as a new cellular therapy. However, CASCs are transplanted into a hostile environment, with elevated levels of advanced glycation end products (AGEs), which may affect their regenerative potential. In this study, we hypothesize that pyridoxamine (PM), a vitamin B6 derivative, could further enhance the regenerative capacities of CASCs transplanted after MI by reducing AGEs’ formation. Methods and Results: MI was induced in rats by ligation of the left anterior descending artery. Animals were assigned to either no therapy (MI), CASCs transplantation (MI + CASCs), or CASCs transplantation supplemented with PM treatment (MI + CASCs + PM). Four weeks post-surgery, global cardiac function and infarct size were improved upon CASCs transplantation. Interstitial collagen deposition, evaluated on cryosections, was decreased in the MI animals transplanted with CASCs. Contractile properties of resident left ventricular cardiomyocytes were assessed by unloaded cell shortening. CASCs transplantation prevented cardiomyocyte shortening deterioration. Even if PM significantly reduced cardiac levels of AGEs, cardiac outcome was not further improved. Conclusion: Limiting AGEs’ formation with PM during an ischemic injury in vivo did not further enhance the improved cardiac phenotype obtained with CASCs transplantation. Whether AGEs play an important deleterious role in the setting of stem cell therapy after MI warrants further examination.

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“…In this context, our research group previously showed that a chronic increase in HMW-AGE levels in vivo leads to cardiac dysfunction in rats, characterised by interstitial fibrosis, myocardial wall hypertrophy, and increased left ventricular pressure [ 23 ]. At the cellular level, chronic exposure to high levels of HMW-AGEs induces cardiomyocyte remodelling, resulting in impaired cellular function [ 24 ]. In addition, we have previously shown that the chronic administration of HMW-AGEs disturbs the vasomotor balance in rat aortae which is the result of increased oxidative stress [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Acute Exposure to Glycated Proteins Impaired in the Endothelium-Dependent Aortic Relaxation: A Matter of Oxidative Stress

D'Haese

Deluyker

Bito

2022

IJMS

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Chronically increased levels of high molecular weight advanced glycation end products (HMW-AGEs) are known to induce cardiovascular dysfunction. Whether an acute increase in HMW-AGE levels affects vascular function remains unknown. In this study, we examined whether acute exposure to HMW-AGEs disturbs aortic vasomotor function. Aortae were obtained from healthy male rats and were acutely pre-treated with HMW-AGEs in organ baths. Aortic relaxation responses to cumulative doses of acetylcholine (ACh), in the presence or absence of superoxide dismutase (SOD), were measured after precontraction with phenylephrine (PE). Furthermore, levels of 3-nitrotyrosine were evaluated on aortic paraffine sections. In our study, we show that acute exposure to HMW-AGEs significantly decreases the aortic relaxation response to ACh. SOD pre-treatment prevents acute HMW-AGEs-induced impairment by limiting superoxide formation. In conclusion, our data demonstrate that acute exposure to HMW-AGEs causes adverse vascular remodelling, characterised by disturbed vasomotor function due to increased oxidative stress. These results create opportunities for future research regarding the acute role of HMW-AGEs in cardiovascular dysfunction.

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Glycolaldehyde-Derived High-Molecular-Weight Advanced Glycation End-Products Induce Cardiac Dysfunction through Structural and Functional Remodeling of Cardiomyocytes

Abstract: This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Cited by 6 publications

References 49 publications

Extracellular Vesicles in Diabetic Cardiomyopathy—State of the Art and Future Perspectives

Extracellular Vesicles in Diabetic Cardiomyopathy—State of the Art and Future Perspectives

Combinational Therapy of Cardiac Atrial Appendage Stem Cells and Pyridoxamine: The Road to Cardiac Repair?

Acute Exposure to Glycated Proteins Impaired in the Endothelium-Dependent Aortic Relaxation: A Matter of Oxidative Stress

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