Novel Insights in the Metabolic Syndrome-induced Oxidative Stress and Inflammation-mediated Atherosclerosis

Varghese, Johnna F.; Patel, R. B.; Yadav, Umesh C. S.

doi:10.2174/1573403x13666171009112250

Cited by 73 publications

(58 citation statements)

References 97 publications

(111 reference statements)

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“…Nearly one‐half of postmenopausal women develop osteoporosis, but menopause also increases incidence of other comorbidities including coronary artery disease, certain cancers, chronic obstructive pulmonary disease, stroke, and dementia . It is tempting to speculate that the proinflammatory T cells produced by E 2 loss also contribute to the pathogenesis of these conditions because all these conditions are known to be caused by both chronic inflammation and metabolic syndrome . In conclusion, our studies establish a new regulatory circuit between E 2 , the immune system, and the skeletal system.…”

Section: Discussionmentioning

confidence: 99%

Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice

Cline-Smith

Axelbaum

Shashkova

et al. 2020

Journal of Bone and Mineral Research

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The loss of estrogen (E2) initiates a rapid phase of bone loss leading to osteoporosis in one‐half of postmenopausal women, but the mechanism is not fully understood. Here, we show for the first time how loss of E2 activates low‐grade inflammation to promote the acute phase of bone catabolic activity in ovariectomized (OVX) mice. E2 regulates the abundance of dendritic cells (DCs) that express IL‐7 and IL‐15 by inducing the Fas ligand (FasL) and apoptosis of the DC. In the absence of E2, DCs become long‐lived, leading to increased IL‐7 and IL‐15. We find that IL‐7 and IL‐15 together, but not alone, induced antigen‐independent production of IL‐17A and TNFα in a subset of memory T cells (TMEM). OVX of mice with T‐cell–specific ablation of IL15RA showed no IL‐17A and TNFα expression, and no increase in bone resorption or bone loss, confirming the role of IL‐15 in activating the TMEM and the need for inflammation. Our results provide a new mechanism by which E2 regulates the immune system, and how menopause leads to osteoporosis. The low‐grade inflammation is likely to cause or contribute to other comorbidities observed postmenopause. © 2020 American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 99%

Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice

Cline-Smith

Axelbaum

Shashkova

et al. 2020

Journal of Bone and Mineral Research

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“…It plays a significant role in the pathogenesis and pathophysiology of different diseases, including cardiovascular, neurodegenerative, oncological, inflammatory, etc. (22,23). Thus, the role of antioxidants in the prevention and treatment of oxidative stress-related conditions is continuously increasing and many efforts have been targeted on the synthesis of new antioxidants with low cytotoxicity (24)(25)(26).…”

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confidence: 99%

Synthesis, in vitro safety and antioxidant activity of new pyrrole hydrazones

et al. 2020

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Six new N-pyrrolylhydrazide hydrazones were synthesized under micro synthesis conditions, assuring about 59–93 % yield, low harmful emissions and reagent economy. The structures of the new compounds were elucidated by melting points, TLC characteristics, IR, 1H and 13C NMR spectral data followed by MS data. The purity of the obtained compounds was proven by the corresponding elemental analyses. “Lipinski’s rule of five” parameters were applied for preliminary evaluation of the pharmacokinetic properties of the target molecules. The initial in vitro safety screening for cytotoxicity (on HepG2 cells) and hemocompatibility (hemolysis assay) showed good safety of the new compounds, where ethyl 5-(4-bromophenyl)-1-(1-(2-(4-hydroxy-3-methoxybenzylidene)-hydrazineyl)-1-oxo-3-phenylpropan-2-yl)-2-methyl-1H-pyr-role-3-carboxylate (4d) and ethyl 5-(4-bromophenyl)-1-(1-(2-(2-hydroxybenzylidene)hydrazineyl)-1-oxo-3-phenylpropan--2-yl)-2-methyl-1H-pyrrole-3-carboxylate (4a) were the least toxic. The antioxidant activity in terms of radical scavenging activity (DPPH test) and reducing ability (ABTS) was also evaluated. The antioxidant protective potential of the compounds was next determined in different in vitro cellular-based models, revealing compounds 4d and 3 [ethyl 5-(4-bromophenyl)-1-(1-hydrazineyl-1-oxo-3-phenylpropan-2-yl)-2-methyl-1H-pyrrole-3-carboxylate] as the most promising compounds, with 4d having better safety profile.

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“…However, recent advances suggest that AS is a multifactorial and multigenic inflammatory condition in the arterial wall [31][32]. Some of the major risk factors for the development of AS, including hyperglycemia, dyslipidemia, and hyperinsulinemia, along with hypertension, smoking, and physical inactivity, are classified as metabolic syndrome, persistent presence of various atherogenic molecules instigates a hypoxic environment along with oxidative stress [33]. These changes could contribute towards enhanced ROS production in the cells, which activating and augmenting various inflammatory pathways, leading to the occurrence and development of AS [34].…”

Section: Discussionmentioning

confidence: 99%

Body mass index influence the association between triglyceride-glucose index and atherosclerosis in community population: the cardiometabolic risk in Chinese (CRC) study

Wang

Qiu

Meng

et al. 2020

Preprint

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Background: Cardiovascular disease (CVD) is an universal problem in modern society. Atherosclerosis is the leading cause of CVD resulting in high rate of mortality in the population. The study aimed to examine the association of triglyceride-glucose (TyG) index, a novel marker of insulin resistance, with atherosclerosis in Chinese adults, and the effects of different body mass index (BMI) levels on this relationship.Methods: The study samples were from a community-based health examination survey in central China. A total of 4729 apparently healthy Chinese men and women were included. TyG index was calculated as ln[fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2]. Parameters of vascular damage, including carotid-femoral pulse wave velocity (cfPWV), carotid-radial pulse wave velocity (crPWV), carotid-dorsalis pedis pulse wave velocity (cdPWV) were measured.Results: After adjustment for conventional risk factors, TyG index was significantly associated with peripheral arterial stiffness (cdPWV>10.57cm/s or crPWV>11.12cm/s), however, TyG index was not associated with central arterial stiffness, measured by cfPWV. Moreover, we found significant interactions between TyG index and BMI in relation to crPWV and cdPWV. Risk for crPWV and cdPWV elevation was significantly decreased across increasing quartiles of TyG index under different BMI levels (P<0.001). There was a dose-response relationship of TyG index with crPWV and cdPWV in the normal-weight and overweight groups, with the most obvious in the normal-weight individuals. However, the dose-response relationship was not existed among the obesity group where the increase of TyG index did not significantly rise the risk of high crPWV and cdPWV.Conclusions: TyG index, a simple measure reflecting insulin resistance, might be useful to early identify individuals at a high risk of developing atherosclerosis. Increased BMI weakened the effect of TyG index on crPWV and cdPWV, indicating that the value of TyG index in assessing the risk of atherosclerosis in obese people maybe easily ignored, however, TyG index can better reflect the risk of atherosclerosis in normal-weight adults.

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Novel Insights in the Metabolic Syndrome-induced Oxidative Stress and Inflammation-mediated Atherosclerosis

Cited by 73 publications

References 97 publications

Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice

Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice

Synthesis, in vitro safety and antioxidant activity of new pyrrole hydrazones

Body mass index influence the association between triglyceride-glucose index and atherosclerosis in community population: the cardiometabolic risk in Chinese (CRC) study

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