Endothelial Dysfunction in Type 2 Diabetes Mellitus

Dhananjayan, R; Koundinya, K. S. Srivani; Malati, T.; Kutala, Vijay Kumar

doi:10.1007/s12291-015-0516-y

Cited by 109 publications

(85 citation statements)

References 64 publications

(54 reference statements)

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“…Chronic inflammation and oxidative stress are regarded as pathophysiologic mechanisms of type 2 diabetes, which impair glucose metabolism and increase risks of other metabolic complications [15,16]. In our study, before treatment, we found indictors of inflammation including IL-6 and TNF-α increased and biomarkers of oxidative stress like MDA and SOD varied significantly in rats model.…”

Section: Discussionsupporting

confidence: 48%

Role of Ketotifen on metabolic profiles, inflammation and oxidative stress in diabetic rats

et al. 2017

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Abstract. We aim to explore effects of Ketotifen on metabolic profiles, inflammation and oxidative stress. Sprague Dawley (SD) male rats were randomly divided into normal control group (NC) and experimental groups, and experimental group rats were fed with high-sugar and fat diet for 6 weeks. Then, experimental group rats were divided into diabetes group (DM) and ketotifen treatment group (KT). KT group was given ketotifen via Intragastric for 8 weeks with the dosage of 0.09 mg/kg/d. Fasting plasma glucose (FPG) was measured using glucose oxidase-phenol amino phenazone method. Fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were tested by enzyme-linked immunosorbent assay. Malondialdehyde (MDA) and superoxide dismutase (SOD) were quantified by spectrophotometer method. Before Ketotifen administration, compared with NC group, DM and KT groups showed significantly high levels of body weight,

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Section: Discussionsupporting

confidence: 48%

Role of Ketotifen on metabolic profiles, inflammation and oxidative stress in diabetic rats

et al. 2017

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“…Obesity is described to result from increased energy intake with subsequent reduced physical activities [2]. It is a metabolic condition of chronic low-grade inflammation, associated with high levels of inflammatory markers, such as CRP, IL-6, and TNF-α [2,6]. In this, the low-grade chronic inflammation is characterized by a variety of chronic diseases, including cardiovascular disease, diabetes, hypertension, nonalcoholic fatty liver disease [2], hypercholesterolemia, asthma, arthritis, some cancers, and general poor health condition, and hence represents a significant burden on the global healthcare system [5].…”

Section: Introductionmentioning

confidence: 99%

“…The global prevalence of obesity increases the potential risk factors for developing chronic metabolic syndromes [7]. Significant increase in bodyweight is highly attributed to several metabolic complications, such as cardiovascular disease, pulmonary complications, diabetes, and some certain cancers [8,9], leading to diminished life expectancy [2,6]. Furthermore, overweight or obese pregnant women have increased risks of developing offspring with obesity and its other related metabolic complications in future life, which justifies a transgenerational cycle of obesity [5].…”

Section: Introductionmentioning

confidence: 99%

“…Endothelial dysfunction (ED) results from an imbalance in the production of vasodilatory agents, such as nitric oxide (NO), endothelial-derived hyperpolarizing factors (EDHF), prostacyclin (PGI2), and vasoconstricting agents, including prostaglandin (PGH2), endothelin-1 (ET-1), and angiotensin-II (Ang-II). Under normal physiology, the balanced release of contracting and endothelial-derived relaxing factors is maintained [6]. Alterations in this balance predispose the vascular endothelium towards prothrombotic and proatherogenic states, resulting in platelet activation, leukocyte adherence, vasoconstriction, pro-oxidation, mitogenesis, vascular inflammation, impaired coagulation, atherosclerosis, and thrombosis with subsequent cardiovascular diseases [6].…”

Section: Introductionmentioning

confidence: 99%

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Endothelial Dysfunction in Obesity-Induced Inflammation: Molecular Mechanisms and Clinical Implications

et al. 2020

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Obesity is characterized by the excessive deposition of fat that may interfere with the normal metabolic process of the body. It is a chronic condition associated with various metabolic syndromes, whose prevalence is grossly increasing, and affects both children and adults. Accumulation of excessive macronutrients on the adipose tissues promotes the secretion and release of inflammatory mediators, including interleukin-6 (IL-6), interleukin 1β, tumor necrotic factor-α (TNF-α), leptin, and stimulation of monocyte chemoattractant protein-1 (MCP-1), which subsequently reduce the production of adiponectin thereby initiating a proinflammatory state. During obesity, adipose tissue synthesizes and releases a large number of hormones and cytokines that alter the metabolic processes, with a profound influence on endothelial dysfunction, a situation associated with the formation of atherosclerotic plaque. Endothelial cells respond to inflammation and stimulation of MCP-1, which is described as the activation of adhesion molecules leading to proliferation and transmigration of leukocytes, which facilitates their increase in atherogenic and thromboembolic potentials. Endothelial dysfunction forms the cornerstone of this discussion, as it has been considered as the initiator in the progression of cardiovascular diseases in obesity. Overexpression of proinflammatory cytokines with subsequent reduction of anti-inflammatory markers in obesity, is considered to be the link between obesity-induced inflammation and endothelial dysfunction. Inhibition of inflammatory mechanisms and management and control of obesity can assist in reducing the risks associated with cardiovascular complications.

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“…Endothelial dysfunction is characterized by an imbalance in the production of vasodilator factors. The imbalance of these factors consequently results in vascular inflammation, disease progression, and end organ damage in T2DM . The endothelium was earlier perceived as an inactive, inert barrier between tissues and blood.…”

Section: Introductionmentioning

confidence: 99%

miR‐181a/b‐5p regulates human umbilical vein endothelial cell angiogenesis by targeting PDGFRA

Sun

Yin

Kuang

2019

Cell Biochemistry & Function

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Type 2 diabetes mellitus (T2DM) is a growing burden in low-and middle-income countries. Changing lifestyles and lack of physical activity are some of the reasons contributing to this epidemic increase. Co-morbidities associated with T2DM are largely due to the complications which arise as a consequence of endothelial dysfunction. Platelet derived growth factor-alpha (PDGFRA) is a protein responsible for cell proliferation, angiogenesis, migration and invasion. Increased levels of PDGFRA have been reported in T2DM. This study assessed the epigenetic regulation of PDGFRA through micro-Using a bioinformatics-based approach, we assessed the binding of miR-181a/b-5p to PDGFRA. Experimentally, this binding was confirmed using a dual luciferase reporter assay. Further, we overexpressed miR-181a/b-5p in Human umbilical vein endothelial cells (HUVECs) and the influence of over-expression on cell proliferation, migration and angiogenesis was assessed using in-vitro approaches. The influence of miR-181a/b-5p over expression on cellular apoptosis was ascertained using a TUNEL assay with concomitant changes being observed in the levels of Bcl-2 and cleaved Caspase-3.In HUVECs, PDGFRA is a direct target for miR-181a/b-5p.Over expression of miR-181a/b-5p decreased cellular proliferation, migration, invasion, and tube formation-a surrogate marker for angiogenesis. miR-181a/b-5p may be used as a therapeutic intervention to restrict uncontrolled levels of PDGFRA and thereby rescue the phenotypes of increased cell proliferation, migration, invasion and tube formation. miR-181a/b negatively regulates PDGFRA levels.Significance of the study: T2DM and its associated complications emerge from endothelial dysfunction. The associated phenotypes are regulated by a number of proteins, one such member being, PDGFRA. PDGFRA is in turn regulated by miR-181a/b-5p.Complementation with miR-181a/b-5p resulted in reversion of phenotypes. Thus, miR-181a/b-5p-mediated suppression of PDGFRA may be used as a therapeutic intervention in the management of type 2 diabetes. K E Y W O R D S angiogenesis, HUVECs, miR-181a-5p, miR-181b-5p, PDGFRA

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Endothelial Dysfunction in Type 2 Diabetes Mellitus

Cited by 109 publications

References 64 publications

Role of Ketotifen on metabolic profiles, inflammation and oxidative stress in diabetic rats

Role of Ketotifen on metabolic profiles, inflammation and oxidative stress in diabetic rats

Endothelial Dysfunction in Obesity-Induced Inflammation: Molecular Mechanisms and Clinical Implications

miR‐181a/b‐5p regulates human umbilical vein endothelial cell angiogenesis by targeting PDGFRA

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