scholarly journals Epigenetic regulation in diabetic vascular complications

2019 ◽  
Vol 63 (4) ◽  
pp. R103-R115 ◽  
Author(s):  
Jiayu Jin ◽  
Xinhong Wang ◽  
Xiuling Zhi ◽  
Dan Meng
Keyword(s):  
Endothelial Dysfunction ◽  
Epigenetic Regulation ◽  
Epigenetic Modification ◽  
Vascular Complications ◽  
Integrated System ◽  
Metabolic Memory ◽  
Diabetic Patients ◽  
Epigenetic Alterations ◽  
Diabetic Vascular Complications ◽  
Legacy Effect

Cardiovascular disease (CVD), the main complication of diabetes mellitus (DM), accounts for a high percentage of mortality in diabetic patients. Endothelial dysfunction is a major causative event in the pathogenesis of diabetes-related vascular disease and the earliest symptom of vascular injury. Epigenetic modification plays a key role in the initiation, maintenance, and progression of both endothelial dysfunction and diabetes. Epigenetic alterations respond to the environment and mediate the ‘legacy effect’ of uncontrolled hyperglycaemia early in the disease despite thorough glycaemic control in a phenomenon called metabolic memory. Therefore, an understanding of the integrated system of different epigenetic mechanisms in DM and its vascular complications is urgently needed. This review summarizes aberrant epigenetic regulation under diabetic conditions, including histone modifications, DNA methylation, and non-coding RNAs (ncRNAs). Understanding the connections between these processes and DM may reveal a novel potential therapeutic target for diabetic vascular complications.

Relationship of Soluble RAGE and RAGE Ligands HMGB1 and EN-RAGE to Endothelial Dysfunction in Type 1 and Type 2 Diabetes Mellitus

2012 ◽  
Vol 120 (05) ◽  
pp. 277-281 ◽  
Author(s):  
J. Škrha Jr ◽  
M. Kalousová ◽  
J. Švarcová ◽  
A. Muravská ◽  
J. Kvasnička ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Advanced Glycation Endproducts ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Glycation Endproducts ◽  
Diabetic Vascular Complications ◽  
Soluble Rage

AbstractReceptor for advanced glycation endproducts (RAGE) plays the essential role in the pathogenesis of diabetic vascular complications. The aim of the study was to compare concentration of soluble RAGE and its ligands (EN-RAGE and HMGB1) with different biochemical parameters in Type 1 (T1DM) and Type 2 (T2DM) diabetes mellitus.Total number of 154 persons (45 T1DM, 68 T2DM, 41 controls) was examined and concentrations of sRAGE, EN-RAGE and HMGB1 were measured and compared to diabetes control, albuminuria, cell adhesion molecules and metalloproteinases (MMPs).Mean serum sRAGE concentration was higher in T1DM as compared to controls (1137±532 ng/l vs. 824±309 ng/l, p<0.01). Similarly, EN-RAGE was significantly higher in both diabetic groups (p<0.001) and HMGB1 concentrations were elevated in T2DM patients (p<0.01). Significant relationship was found between MMP9 and HMGB1 and EN-RAGE in diabetic patients. Inverse relationship was observed between MMP2 and MMP9 in both types of diabetic patients (r= − 0.602, p<0.002 and r= − 0.771, p<0.001). Significant positive correlation was found between sRAGE and ICAM-1, VCAM-1 or vWF (p<0.01 to p<0.001).We conclude that serum sRAGE and RAGE ligands concentrations reflect endothelial dysfunction developing in diabetes.

scholarly journals Novel insights into DNA methylation and its critical implications in diabetic vascular complications

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
Jia Zheng ◽  
Jing Cheng ◽  
Qian Zhang ◽  
Xinhua Xiao
Keyword(s):  
Dna Methylation ◽  
Vascular Complications ◽  
Metabolic Memory ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Diabetic Vascular Complications ◽  
Underlying Mechanisms ◽  
Prevention Of Diabetes

Recent epidemiological and clinical studies have shown that type 2 diabetic patients can develop diabetic vascular complications even after intensive glycaemic control. It has been suggested that this phenomenon could be explained by the hypothesis of ‘metabolic memory’. The underlying mechanisms between these enduring effects and the prior hyperglycaemic state are still not well understood. Preliminary studies demonstrate that hyperglycaemia can regulate gene expression by epigenetic modifications, such as DNA methylation, which can persistently exist even after glucose normalization. Increasing evidence shows that epigenetic mechanisms may play a substantial role in the pathophysiology of diabetes and its associated vascular complications, including atherosclerosis, diabetic cardiomyopathy (DCM), nephropathy and retinopathy. In this review, we will examine the growing role of DNA methylation in diabetes and its vascular complications, thus it can provide critical implications for the early prevention of diabetes and its vascular complications.

scholarly journals Roles of Endovascular Calyx Related Enzymes in Endothelial Dysfunction and Diabetic Vascular Complications

2020 ◽  
Vol 11 ◽  
Author(s):  
Zhi Li ◽  
Ning Wu ◽  
Jing Wang ◽  
Quanbin Zhang
Keyword(s):  
Quality Of Life ◽  
Hyaluronic Acid ◽  
Endothelial Dysfunction ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Complications Of Diabetes ◽  
Diabetic Vascular Complications ◽  
Hyaluronic Acid Synthase ◽  
The Relationship

In recent years, the number of diabetic patients has rapidly increased. Diabetic vascular complications seriously affect people’s quality of life. Studies found that endothelial dysfunction precedes the vascular complications of diabetes. Endothelial dysfunction is related to glycocalyx degradation on the surface of blood vessels. Heparanase (HPSE), matrix metalloproteinase (MMP), hyaluronidase (HYAL), hyaluronic acid synthase (HAS), and neuraminidase (NEU) are related to glycocalyx degradation. Therefore, we reviewed the relationship between endothelial dysfunction and the vascular complications of diabetes from the perspective of enzymes.

Susceptibility of Glutathione--S-Transferase Polymorphism to CVD Development in Type 2 Diabetes Mellitus - A Review

2021 ◽  
Vol 21 ◽  
Author(s):  
Santhi Priya Sobha ◽  
Kumar Ebenezar
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Metabolic Disorder ◽  
Vascular Complications ◽  
Clinical Importance ◽  
Diabetic Patients ◽  
Diabetic Vascular Complications ◽  
Metabolic Conditions ◽  
Gst Polymorphism ◽  
Gene Status

Background: Metabolic disorder affects normal homeostasis and can lead to the development of diseases. Diabetes mellitus is the most common metabolic disorder, and a cluster of metabolic conditions can lead to cardiovascular disease (CVD) development. Diabetes mellitus and CVD are closely related, with oxidative stress, playing a major role in the pathophysiology. Glutathione-S-Transferases (GST) potentially play an important role by reducing oxidative stress and is found to be the underlying pathophysiology in the development of diabetes, cardiovascular diseases (CVD), etc. Objectives: In this review, the role of GST genetic variant in the development of diabetes mellitus, CVD and diabetic vascular complications has been focused. Results: Based on the literature, it is evident that the GST can act as an important biochemical tool providing significant evidence regarding oxidative stress predominant in the development of diseases. Analysis of GST gene status, particularly detection of GSTM1 and GSTT1 null mutations and GSTP1 polymorphism, have clinical importance. Conclusion: The analysis of GST polymorphism may help identify the people at risk and provide proper medical management. Genotyping of GST gene would be a helpful biomarker for early diagnosis of CVD development in DM and also in CVD cases. More studies focusing on the association of GST polymorphism with CVD development in diabetic patients will help us determine the pathophysiology better.

Icariin Attenuates High Glucose-Induced Apoptosis, Oxidative Stress, and Inflammation in Human Umbilical Venous Endothelial Cells

Planta Medica ◽  
2019 ◽  
Vol 85 (06) ◽  
pp. 473-482 ◽  
Author(s):  
Si Sun ◽  
Le Liu ◽  
Xiaojun Tian ◽  
Yanghongyun Guo ◽  
Yingkang Cao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
High Glucose ◽  
Vascular Endothelial Cells ◽  
Reactive Oxygen Species Generation ◽  
Vascular Complications ◽  
Flavonoid Glycoside ◽  
Inflammatory Factors ◽  
Diabetic Vascular Complications ◽  
Induced Apoptosis

AbstractEndothelial dysfunction is closely associated with diabetic complications. Icariin, a flavonoid glycoside isolated from the Epimedium plant species, exhibits antidiabetic properties. However, its impact on endothelial function remains poorly understood, particularly under hyperglycemia. In this study, we investigated the potential protective effect of icariin on high glucose-induced detrimental effects on vascular endothelial cells. Human umbilical venous endothelial cells were incubated in media containing 5.5 mM glucose (normal glucose) or 25 mM glucose (high glucose) in the presence or absence of 50 µM icariin for 72 h. We found that high glucose markedly induced cell apoptosis, enhanced reactive oxygen species generation, and elevated expression levels of inflammatory factors and cell adhesion molecules, which were greatly subdued by icariin supplementation. In conclusion, icariin exerted a beneficial effect on high glucose-induced endothelial dysfunction. This new finding provides a promising strategy for future treatment of diabetic vascular complications.

scholarly journals Association between Beta2-Adrenergic Receptor Agonists and the Risk of Vascular Complications in Diabetic Patients: A Population-Based Cohort Study

2019 ◽  
Vol 8 (8) ◽  
pp. 1145 ◽  
Author(s):  
Lee ◽  
Lee ◽  
Oh ◽  
Park ◽  
Jung ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Adrenergic Receptor ◽  
Human Subjects ◽  
Vascular Complications ◽  
Population Based ◽  
Vascular Complication ◽  
Control Group ◽  
Diabetic Patients ◽  
Protective Effects ◽  
Diabetic Vascular Complications

Beta2-adrenergic receptor (β2AR) agonists can have protective effects targeting macrophage activation, but research on human subjects has not been done. This study was designed to assess the relationship between the use of β2AR agonists and diabetic vascular complications. Using data from the Korean National Health Insurance Service, adults first diagnosed with diabetes in 2004 (n = 249,222) were followed up until 31 December 2015. Propensity score matching was performed between case and control groups (n = 5179 in each), and multivariate analysis was conducted. The β2AR agonist group was divided into quartiles according to the duration of β2AR agonist use. During the follow-up, the incidence of vascular complications gradually decreased as the duration of β2AR agonist administration increased. Multivariate analysis revealed that the hazard ratio for all composite vascular complications was 0.80 (95% CI, 0.75–0.86, p < 0.001) in the longest quartile of β2AR agonist use as compared with the control group after adjusting for confounding variables. The association between the duration of β2AR agonist use and the risk of each vascular complication including cerebrovascular, peripheral vascular, peripheral neural, renal, and ophthalmic complications was consistent, and the risks were significantly lower in the longest users than the control group. Long-term use of β2AR agonists may exert a protective effect against diabetic vascular complications.

scholarly journals Plasma osteoprotegerin levels are associated with glycaemic status, systolic blood pressure, kidney function and cardiovascular morbidity in type 1 diabetic patients

2006 ◽  
Vol 154 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Lars Melholt Rasmussen ◽  
Lise Tarnow ◽  
Troels Krarup Hansen ◽  
Hans-Henrik Parving ◽  
Allan Flyvbjerg
Keyword(s):  
Blood Pressure ◽  
Type 1 Diabetes ◽  
Systolic Blood Pressure ◽  
Kidney Function ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Diabetic Vascular Complications ◽  
Patients With Diabetes ◽  
Type 1 Diabetic Patients

Objective: The bone-related peptide osteoprotegerin (OPG) has recently been found in increased amounts in the vasculature in diabetes. It is produced by vascular smooth muscle and endothelial cells, and may be implicated in the development of vascular calcifications. OPG is present in the circulation, where increased amounts have been observed in patients with diabetes. In this study, we examined whether plasma OPG is associated with the glycaemic and vascular status of patients with type 1 diabetes. Methods: Two gender-, age- and duration-comparable groups of type 1 diabetic patients either with (n = 199) or without (n = 192) signs of diabetic nephropathy were studied. Plasma OPG was determined by an ELISA. Results: The plasma OPG concentration was significantly higher in patients with nephropathy than those without (3.11 (2.49–3.99) vs 2.57 (2.19–3.21) (median (interquartiles), ng/ml), P < 0.001). Plasma OPG correlated with haemoglobin A1c (HbA1c), systolic blood pressure and age in both groups and, in addition, with kidney function in the nephropathic group. These correlations remained significant in multivariate models. In addition, we found that plasma OPG concentrations were increased among patients with cardiovascular diseases (CVD), both in the normoalbuminuric and the nephropathic groups. The differences between nephropathic and normoalbuminuric, as well as subgroups with and without CVD, could largely be ascribed to changes in HbA1c, age, systolic blood pressure and creatinine. Conclusion: OPG is associated with glycaemic control and CVD in patients with type 1 diabetes, compatible with the hypothesis that OPG is associated with the development of diabetic vascular complications.

scholarly journals Portulaca oleraceaAmeliorates Diabetic Vascular Inflammation and Endothelial Dysfunction in db/db Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
An Sook Lee ◽  
Yun Jung Lee ◽  
So Min Lee ◽  
Jung Joo Yoon ◽  
Jin Sook Kim ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Plasma Level ◽  
Vascular Inflammation ◽  
Folk Medicine ◽  
Vascular Complications ◽  
Hdl Cholesterol ◽  
Insulin Level ◽  
Edible Plant ◽  
Diabetic Vascular Complications ◽  
Glucose Plasma

Type 2 diabetes is associated with significantly accelerated rates of micro- and macrovascular complications such as diabetic vascular inflammation and endothelial dysfunction. In the present study, we investigated the protective effect of the aqueous extract ofPortulaca oleraceaL. (AP), an edible plant used as a folk medicine, on diabetic vascular complications. The db/db mice were treated with AP (300 mg/kg/day, p.o.) for 10 weeks, and AP treatment markedly lowered blood glucose, plasma triglyceride, plasma level of LDL-cholesterol, and systolic blood pressure in diabetic db/db mice. Furthermore, AP significantly increased plasma level of HDL-cholesterol and insulin level. The impairment of ACh- and SNP-induced vascular relaxation of aortic rings were ameliorated by AP treatment in diabetic db/db mice. This study also showed that overexpression of VCAM-1, ICAM-1, E-selectin, MMP-2, and ET-1 were observed in aortic tissues of untreated db/db mice, which were significantly suppressed by treatment with AP. We also found that the insulin immunoreactivity of the pancreatic islets remarkably increased in AP treated db/db mice compared with untreated db/db mice. Taken together, AP suppresses hyperglycemia and diabetic vascular inflammation, and prevents the development of diabetic endothelial dysfunction for the development of diabetes and its vascular complications.

R-(+)-α-lipoic acid inhibits endothelial cell apoptosis and proliferation: involvement of Akt and retinoblastoma protein/E2F-1

2007 ◽  
Vol 293 (3) ◽  
pp. E681-E689 ◽  
Author(s):  
Michaela Artwohl ◽  
Kathrin Muth ◽  
Karin Kosulin ◽  
Rainer de Martin ◽  
Thomas Hölzenbein ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Protein Expression ◽  
Lipoic Acid ◽  
Kinase Inhibitors ◽  
Vascular Complications ◽  
Retinoblastoma Protein ◽  
Cell Cycle Distribution ◽  
Diabetic Patients ◽  
Tnf Α

Lipoic acid was recently demonstrated to improve endothelial dysfunction or retinopathy not only in rats but also in diabetic patients. We tested the hypothesis that R-(+)-α-lipoic acid (LA) directly affects human endothelial cell (EC) function (e.g., apoptosis, proliferation, and protein expression), independent of the cells' vascular origin. Macrovascular EC (macEC), isolated from umbilical (HUVEC) and adult saphenous veins and from aortae, as well as microvascular EC (micEC) from retinae, skin, and uterus, were exposed to LA (1 μmol/l–1 mmol/l) with/without different stimuli (high glucose, TNF-α, VEGF, wortmannin, LY-294002). Apoptosis, proliferation, cell cycle distribution, and protein expression were determined by DNA fragmentation assays, [3H]thymidine incorporation, FACS, and Western blot analyses, respectively. In macro- and microvascular EC, LA (1 mmol/l) reduced ( P < 0.05) basal (macEC, −36 ± 4%; micEC, −46 ± 6%) and stimulus-induced (TNF-α: macEC, −75 ± 11%; micEC, −68 ± 13%) apoptosis. In HUVEC, inhibition of apoptosis by LA (500 μmol/l) was paralleled by reduction of NF-κB. LA's antiapoptotic activity was reduced by PI 3-kinase inhibitors (wortmannin, LY-294002), being in line with LA-induced Akt phosphorylation (Ser437, +159 ± 43%; Thr308, +98 ± 25%; P < 0.01). LA (500 μmol/l) inhibited ( P < 0.001) proliferation of macEC (−29 ± 3%) and micEC (−29 ± 3%) by arresting the cells at the G1/S transition due to an increased ratio of cyclin E/p27Kip (4.2-fold), upregulation of p21WAF-1/Cip1 (+104 ± 21%), and reduction of cyclin A (−32 ± 11%), of hyperphosphorylated retinoblastoma protein (macEC: −51 ± 7%; micEC: −50 ± 15%), and of E2F-1 (macEC: −48 ± 3%; micEC: −31 ± 10%). LA's ability to inhibit apoptosis and proliferation of ECs could beneficially affect endothelial dysfunction, which precedes manifestation of late diabetic vascular complications.

scholarly journals Mini-review: diabetic renal complications, a potential stinky remedy

2016 ◽  
Vol 310 (2) ◽  
pp. F119-F122 ◽  
Author(s):  
Utpal Sen ◽  
Sathnur Pushpakumar
Keyword(s):  
Therapeutic Potential ◽  
Vascular Complications ◽  
Vital Role ◽  
Diabetic Patients ◽  
Diabetic Vascular Complications ◽  
Number Of Patients ◽  
Matrix Metabolism ◽  
Artery Disease ◽  
Stage Renal Disease ◽  
End Stage

Chronic kidney disease is associated with vasculitis and is also an independent risk factor for peripheral vascular and coronary artery disease in diabetic patients. Despite optimal management, a significant number of patients progress toward end-stage renal disease (ESRD), a suggestion that the disease mechanism is far from clear. A reduction in hydrogen sulfide (H2S) has been suggested to play a vital role in diabetic vascular complications including diabetic nephropathy (DN). This mini-review highlights the recent findings on the role of H2S in mitigating abnormal extracellular matrix metabolism in DN. A discussion on the development of the newer slow-releasing H2S compounds and its therapeutic potential is also included.

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