Role of ADMA in the pathogenesis of microvascular complications in type 2 diabetes mellitus

Guo, Xinyang; Xing, Yiqiao; Jin, Wei

doi:10.3389/fendo.2023.1183586

Cited by 6 publications

(4 citation statements)

References 118 publications

(89 reference statements)

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“…However, supplementation may be needed in special medical conditions such as malnutrition, burns, wounds, infections, and diabetes, in which L-Arg levels are lower than in healthy individuals ( 46 – 49 ). Furthermore, a metabolomics study found that asymmetric dimethylarginine (ADMA) is elevated in T2DM patients ( 50 , 51 ). ADMA is an analog of L-Arg that inhibits NO synthesis that impairs endothelial function, which leads to atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

L-arginine supplementation abrogates hypoxia-induced virulence of Staphylococcus aureus in a murine diabetic pressure wound model

Baker,

Seo,

Park

et al. 2024

mSphere

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Diabetic foot ulcers (DFUs) are the most common complications of diabetes resulting from hyperglycemia leading to ischemic hypoxic tissue and nerve damage. Staphylococcus aureus is the most frequently isolated bacteria from DFUs and causes severe necrotic infections leading to amputations with a poor 5-year survival rate. However, very little is known about the mechanisms by which S. aureus dominantly colonizes and causes severe disease in DFUs. Herein, we utilized a pressure wound model in diabetic TALLYHO/JngJ mice to reproduce ischemic hypoxic tissue damage seen in DFUs and demonstrated that anaerobic fermentative growth of S. aureus significantly increased the virulence and the severity of disease by activating two-component regulatory systems leading to expression of virulence factors. Our in vitro studies showed that supplementation of nitrate as a terminal electron acceptor promotes anaerobic respiration and suppresses the expression of S. aureus virulence factors through inactivation of two-component regulatory systems, suggesting potential therapeutic benefits by promoting anaerobic nitrate respiration. Our in vivo studies revealed that dietary supplementation of L-arginine (L-Arg) significantly attenuated the severity of disease caused by S. aureus in the pressure wound model by providing nitrate. Collectively, these findings highlight the importance of anaerobic fermentative growth in S. aureus pathogenesis and the potential of dietary L-Arg supplementation as a therapeutic to prevent severe S. aureus infection in DFUs. IMPORTANCE S. aureus is the most common cause of infection in DFUs, often resulting in lower-extremity amputation with a distressingly poor 5-year survival rate. Treatment for S. aureus infections has largely remained unchanged for decades and involves tissue debridement with antibiotic therapy. With high levels of conservative treatment failure, recurrence of ulcers, and antibiotic resistance, a new approach is necessary to prevent lower-extremity amputations. Nutritional aspects of DFU treatment have largely been overlooked as there has been contradictory clinical trial evidence, but very few in vitro and in vivo modelings of nutritional treatment studies have been performed. Here we demonstrate that dietary supplementation of L-Arg in a diabetic mouse model significantly reduced duration and severity of disease caused by S. aureus . These findings suggest that L-Arg supplementation could be useful as a potential preventive measure against severe S. aureus infections in DFUs.

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Section: Discussionmentioning

confidence: 99%

L-arginine supplementation abrogates hypoxia-induced virulence of Staphylococcus aureus in a murine diabetic pressure wound model

Baker,

Seo,

Park

et al. 2024

mSphere

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“…One potential connection between ADMA and ischemic cardiomyopathy is the role of ADMA in promoting endothelial dysfunction, leading to vasoconstriction and reducing blood flow and oxygen delivery to the heart muscle [22]. However, this relationship is most probably multifactorial, involving a complex interplay between endothelial dysfunction, oxidative stress, inflammation, impaired NO signaling, fibrosis, remodeling, hemodynamic effects, and associated comorbidities [22,41].…”

Section: Discussionmentioning

confidence: 99%

High ADMA Is Associated with Worse Health Profile in Heart Failure Patients Hospitalized for Episodes of Acute Decompensation

Vîlcea,

Borta,

Popețiu

et al. 2024

Medicina

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Background and Objectives: episodes of acute decompensation in chronic heart failure (ADHF), a common health problem for the growing elderly population, pose a significant socio-economic burden on the public health systems. Limited knowledge is available on both the endothelial function in and the cardio-metabolic health profile of old adults hospitalized due to ADHF. This study aimed to investigate the connection between asymmetric dimethylarginine (ADMA)—a potent inhibitor of nitric oxide—and key health biomarkers in this category of high-risk patients. Materials and Methods: this pilot study included 83 individuals with a known ADHF history who were admitted to the ICU due to acute cardiac decompensation. Selected cardiovascular, metabolic, haemogram, renal, and liver parameters were measured at admission to the ICU. Key renal function indicators (serum creatinine, sodium, and potassium) were determined again at discharge. These parameters were compared between patients stratified by median ADMA (114 ng/mL). Results: high ADMA patients showed a significantly higher incidence of ischemic cardiomyopathy and longer length of hospital stay compared to those with low ADMA subjects. These individuals exhibited significantly higher urea at admission and creatinine at discharge, indicating poorer renal function. Moreover, their lipid profile was less favorable, with significantly elevated levels of total cholesterol and HDL. However, no significant inter-group differences were observed for the other parameters measured. Conclusions: the present findings disclose multidimensional, adverse ADMA-related changes in the health risk profile of patients with chronic heart failure hospitalized due to recurrent decompensation episodes.

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“…The serum ADMA level was accepted as a marker of endothelial dysfunction because of its high values in coronary artery disease, end-stage renal failure, stroke, hypertension, and DM [98][99][100][101]. In the present moment, there are no drugs targeting ADMA levels in the context of diabetes management [102].…”

Section: Asymmetric Dimethylargininementioning

confidence: 99%

Advances and Perspectives in Relation to the Molecular Basis of Diabetic Retinopathy—A Review

Błaszkiewicz,

Walulik,

Florek

et al. 2023

Biomedicines

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Diabetes mellitus (DM) is a growing problem nowadays, and diabetic retinopathy (DR) is its predominant complication. Currently, DR diagnosis primarily relies on fundoscopic examination; however, novel biomarkers may facilitate that process and make it widely available. In this current review, we delve into the intricate roles of various factors and mechanisms in DR development, progression, prediction, and their association with therapeutic approaches linked to the underlying pathogenic pathways. Specifically, we focus on advanced glycation end products, vascular endothelial growth factor (VEGF), asymmetric dimethylarginine, endothelin-1, and the epigenetic regulation mediated by microRNAs (miRNAs) in the context of DR.

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Role of ADMA in the pathogenesis of microvascular complications in type 2 diabetes mellitus

Cited by 6 publications

References 118 publications

L-arginine supplementation abrogates hypoxia-induced virulence of Staphylococcus aureus in a murine diabetic pressure wound model

L-arginine supplementation abrogates hypoxia-induced virulence of Staphylococcus aureus in a murine diabetic pressure wound model

High ADMA Is Associated with Worse Health Profile in Heart Failure Patients Hospitalized for Episodes of Acute Decompensation

Advances and Perspectives in Relation to the Molecular Basis of Diabetic Retinopathy—A Review

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