Asymmetric Dimethylarginine in Patients with Ascending Aortic Aneurysms

Гаврилюк, Н. Д.; Дружкова, Т. А.; Irtyuga, Olga; Жлоба, А. А.; Subbotina, T. F.; Uspenskiy, Vladimir; Alexeyeva, Nina; Моисеева, О. М.

doi:10.12945/j.aorta.2016.16.025

Cited by 5 publications

(4 citation statements)

References 21 publications

(24 reference statements)

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“…Other plasma biomarkers of BAV aortopathy, such as matrix metalloproteinases (MMPs) and/or tissue inhibitors of metalloproteinases (TIMPs) in BAV patients [ 93 , 94 ] or the existing association between plasma levels of asymmetric dimethylarginine (ADMA), a competitive endogenous inhibitor of NOS, and the diameter of the ascending aorta in patients with aortic aneurysm, have been proposed [ 95 , 96 ]. In addition, an increase in the soluble receptor for advanced glycation end-products (sRAGE) has been identified in plasma of BAV patients with independence of the dilation of the ascending aorta [ 97 ].…”

Section: Is There a Biomarker For Bicuspid Aortopathy?mentioning

confidence: 99%

Update in Biomolecular and Genetic Bases of Bicuspid Aortopathy

Junco-Vicente

Río-García

Martı́n

et al. 2021

IJMS

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Bicuspid aortic valve (BAV) associated with aortopathy is the most common congenital heart disease in the general population. Far from being a simple harmless valve malformation, it can be a complex and heterogeneous disease and a source of chronic and acute pathology (early valvular disease, aneurysm, dissection). In the previous years, intense research has been carried out to find out and understand its mechanisms, but the pathophysiology of the disease is still not fully understood and many questions remain open. Recent studies have discovered several genetic mutations involved in the development of valvular and aortic malformations, but still cannot explain more than 5–10% of cases. Other studies have also focused on molecular alterations and cellular processes (TGF-β pathway, microRNAs, degradation of the extracellular matrix, metalloproteinases, etc.), being a field in constant search and development, looking for a therapeutic target to prevent the development of the disease. Increased knowledge about this multifaceted disorder, derived from both basic and clinical research, may influence the diagnosis, follow-up, prognosis, and therapies of affected patients in the near future. This review focuses on the latest and outstanding developments on the molecular and genetic investigations of the bicuspid aortopathy.

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Section: Is There a Biomarker For Bicuspid Aortopathy?mentioning

confidence: 99%

Update in Biomolecular and Genetic Bases of Bicuspid Aortopathy

Junco-Vicente

Río-García

Martı́n

et al. 2021

IJMS

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“…Recently, evidence of endothelial dysfunction (ED) present in BAV has surfaced ( Vaturi et al, 2011 ; Ali et al, 2014 ; Alegret et al, 2016 ; Gavriliuk et al, 2016 ; Balistreri et al, 2018 ; van de Pol et al, 2019 ). ED stands for the abnormal functioning of the endothelial cells (ECs) that cover the inner surface of blood vessels, the endothelium.…”

Section: Endothelial Dysfunction In Bav Disease: Evidence and Biomarkmentioning

confidence: 99%

“…Therefore, it is hard to deny that ED is probably directly related to BAV and its worse prognosis, especially with aortic dilatation and aortic stenosis ( Vaturi et al, 2011 ; Ali et al, 2014 ; Alegret et al, 2016 ; Gavriliuk et al, 2016 ; Balistreri et al, 2018 ; van de Pol et al, 2019 ). Nevertheless, the pathways that could promote ED and its relevance in BAV are not fully known.…”

Section: Endothelial Dysfunction In Bav Disease: Evidence and Biomarkmentioning

confidence: 99%

“…Based on the latest evidence, ED might be related to BAV and its associated aortopathies ( Vaturi et al, 2011 ; Ali et al, 2014 ; Alegret et al, 2016 ; Gavriliuk et al, 2016 ; Balistreri et al, 2018 ; van de Pol et al, 2019 ). While the mechanisms and pathways involved in this process are not fully elucidated, ED seems to be linked to the progression of BAV disease, leading up to aortopathy and valvular dysfunction.…”

Section: Ed As a Potential Biomarker And Therapeutic Target In Bav DImentioning

confidence: 99%

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Bicuspid Aortic Valve and Endothelial Dysfunction: Current Evidence and Potential Therapeutic Targets

2020

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Bicuspid aortic valve (BAV), the most frequent congenital heart malformation, is characterized by the presence of a two-leaflet aortic valve instead of a three-leaflet one. BAV disease progression is associated with valvular dysfunction (in the form of stenosis or regurgitation) and aortopathy, which can lead to aneurysm and aortic dissection. This morphological abnormality modifies valve dynamics and promotes eccentric blood flow, which gives rise to alterations of the flow pattern and wall shear stress (WSS) of the ascending aorta. Recently, evidence of endothelial dysfunction (ED) in BAV disease has emerged. Different studies have addressed a reduced endothelial functionality by analyzing various molecular biomarkers and cellular parameters in BAV patients. Some authors have found impaired functionality of circulating endothelial progenitors in these patients, associating it with valvular dysfunction and aortic dilation. Others focused on systemic endothelial function by measuring artery flow-mediated dilation (FMD), showing a reduced FMD in BAV individuals. Novel biomarkers like increased endothelial microparticles (EMP), which are related to ED, have also been discovered in BAV patients. Finally, latest studies indicate that in BAV, endothelial-to-mesenchymal transition (EndoMT) may also be de-regulated, which could be caused by genetic, hemodynamic alterations, or both. Different hypothesis about the pathology of ED in BAV are nowadays being debated. Some authors blamed this impaired functionality just on genetic abnormalities, which could lead to a pathological aorta. Nevertheless, thanks to the development of new and high-resolution imaging techniques like 4D flow MRI, hemodynamics has gained great attention. Based on latest studies, alterations in blood flow seem to cause proper modification of the endothelial cells (ECs) function and morphology. It also seems to be associated with aortic dilation and decreased vasodilators expression, like nitric oxide (NO). Although nowadays ED in BAV has been reported by many, it is not clear which its main cause may be. Comprehending the pathways that promote ED and its relevance in BAV could help further understand and maybe prevent the serious consequences of this disease. This review will discuss the ED present in BAV, focusing on the latest evidence, biomarkers for ED and potential therapeutic targets (Figure 1).

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Elevated Levels of ADMA Are Associated with Lower DDAH2 and Higher PRMT1 in LPS-Induced Endometritis Rats

Xiao

Sui

et al. 2017

Inflammation

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Chronic endometritis is a continuous inflammation of uterine endometrium. Recent research has shown that higher asymmetric dimethylarginine (ADMA) levels contribute to endothelial dysfunction. In the present study, we tested whether there is a correlation between endometritis and ADMA in LPS-induced endometritis rat and the mechanisms involved. Thirty-six rats were divided into two groups: blank control group and rat model of endometritis group. The entire infused uterus were removed to observe the changes of histopathology, production of myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, 8-isoprostane, and reactive oxygen species (ROS), and gene expression of dimethylarginine dimethylaminohydrolase 2 (DDAH2), protein-methyl transferase 1 (PRMT1), TNF-α, and IL-6. In endometritis rat group, characteristic histopathologic changes in uteri were observed. The uterine 8-isoprostane, ROS, MPO activity, IL-6 and TNF-α concentrations, PRMT1, IL-6, and TNF-α expressions were significantly elevated, and DDAH2 expression was notably reduced in endometritis group compared with control group. The present findings suggest that elevated levels of ADMA are associated with lower DDAH2 and higher PRMT1 in LPS-induced endometritis rat.

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Asymmetric Dimethylarginine in Patients with Ascending Aortic Aneurysms

Cited by 5 publications

References 21 publications

Update in Biomolecular and Genetic Bases of Bicuspid Aortopathy

Update in Biomolecular and Genetic Bases of Bicuspid Aortopathy

Bicuspid Aortic Valve and Endothelial Dysfunction: Current Evidence and Potential Therapeutic Targets

Elevated Levels of ADMA Are Associated with Lower DDAH2 and Higher PRMT1 in LPS-Induced Endometritis Rats

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