Chronic iron overload intensifies atherosclerosis in apolipoprotein E deficient mice: Role of oxidative stress and endothelial dysfunction

Cardiovascular diseases (CVDs) are the most common cause of morbidity and mortality worldwide. The potential benefits of natural antioxidants derived from supplemental nutrients against CVDs are well known. Remarkably, natural antioxidants exert cardioprotective effects by reducing oxidative stress, increasing vasodilation, and normalizing endothelial dysfunction. Recently, considerable evidence has highlighted an important role played by the synergistic interaction between endothelial nitric oxide synthase (eNOS) and sirtuin 1 (SIRT1) in the maintenance of endothelial function. To provide a new perspective on the role of natural antioxidants against CVDs, we focused on microRNAs (miRNAs), which are important posttranscriptional modulators in human diseases. Several miRNAs are regulated via the consumption of natural antioxidants and are related to the regulation of oxidative stress by targeting eNOS and/or SIRT1. In this review, we have discussed the specific molecular regulation of eNOS/SIRT1-related endothelial dysfunction and its contribution to CVD pathologies; furthermore, we selected nine different miRNAs that target the expression of eNOS and SIRT1 in CVDs. Additionally, we have summarized the alteration of miRNA expression and regulation of activities of miRNA through natural antioxidant consumption.

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Anti-atherosclerotic effect of housefly (Musca domestica) maggot-derived protein-enriched extracts by dampened oxidative stress in apolipoprotein E-deficient mice

RSC Advances ◽

10.1039/c6ra09019b ◽

2016 ◽

Vol 6 (107) ◽

pp. 105363-105370 ◽

Cited By ~ 4

Author(s):

Xiao Mingzhu ◽

Jin Xiaobao ◽

Tang Futian ◽

Wang Lijing ◽

Mao Jianwen ◽

...

Keyword(s):

Oxidative Stress ◽

Apolipoprotein E ◽

Musca Domestica ◽

Developed Countries ◽

Morbidity And Mortality ◽

Deficient Mice

Despitemany therapeutic advances, atherosclerosis remains the leading cause of morbidity and mortality in developed countries.

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Critical Role of Bone Marrow Angiotensin II Type 1 Receptor in the Pathogenesis of Atherosclerosis in Apolipoprotein E–Deficient Mice

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.107.152363 ◽

2008 ◽

Vol 28 (1) ◽

pp. 90-96 ◽

Cited By ~ 49

Author(s):

Daiju Fukuda ◽

Masataka Sata ◽

Nobukazu Ishizaka ◽

Ryozo Nagai

Keyword(s):

Bone Marrow ◽

Angiotensin Ii ◽

Apolipoprotein E ◽

Critical Role ◽

Deficient Mice

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The role of diabetes in the onset and development of endothelial dysfunction

Problems of Endocrinology ◽

10.14341/probl12212 ◽

2020 ◽

Vol 66 (1) ◽

pp. 47-55

Author(s):

Era B. Popyhova ◽

Tatiana V. Stepanova ◽

Dar’ya D. Lagutina ◽

Tatiana S. Kiriiazi ◽

Alexey N. Ivanov

Keyword(s):

Oxidative Stress ◽

Endothelial Dysfunction ◽

Critical Role ◽

Vascular Complications ◽

Glycation End Products ◽

Smooth Muscle Cell Migration ◽

Basic Functions ◽

Cell Migration And Proliferation ◽

Radical Processes

The vascular endothelium performs many functions. It is a key regulator of vascular homeostasis, maintains a balance between vasodilation and vasoconstriction, inhibition and stimulation of smooth muscle cell migration and proliferation, fibrinolysis and thrombosis, and is involved to regulation of platelet adhesion and aggregation. Endothelial dysfunction (ED) plays the critical role in pathogenesis of diabetes mellitus (DM) vascular complications. The purpose of this review was to consider the mechanisms leading to the occurrence of ED in DM. The paper discusses current literature data concerning the role of hyperglycemia, oxidative stress, advanced glycation end products in endothelial alteration. A separate section is devoted to the particularities of the functioning of the antioxidant system and their significance in the development of ED in DM. The analysis of the literature allows to conclude that pathological activation of glucose utilization pathways causes damage of endothelial cells, which is accompanied by disorders of all their basic functions. Metabolic disorders in DM cause a pronounced imbalance of free radical processes and antioxidant defense, accompanied by oxidative stress of endotheliocytes, which contributes to the progression of ED and the development of vascular complications. Many aspects of multicomponent regulatory reactions in the pathogenesis of the development of ED in DM have not been sufficiently studied.

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Dipeptidyl peptidase-4 inhibitor, linagliptin, ameliorates endothelial dysfunction and atherogenesis in normoglycemic apolipoprotein-E deficient mice

Vascular Pharmacology ◽

10.1016/j.vph.2015.08.011 ◽

2016 ◽

Vol 79 ◽

pp. 16-23 ◽

Cited By ~ 32

Author(s):

Hotimah Masdan Salim ◽

Daiju Fukuda ◽

Yasutomi Higashikuni ◽

Kimie Tanaka ◽

Yoichiro Hirata ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Apolipoprotein E ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase 4 ◽

Dipeptidyl Peptidase 4 Inhibitor ◽

Deficient Mice

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Omega 3 Polyunsaturated Fatty Acids Improve Endothelial Dysfunction in Chronic Renal Failure: Role of eNOS Activation and of Oxidative Stress

Nutrients ◽

10.3390/nu9080895 ◽

2017 ◽

Vol 9 (8) ◽

pp. 895 ◽

Cited By ~ 13

Author(s):

Michela Zanetti ◽

Gianluca Gortan Cappellari ◽

Davide Barbetta ◽

Annamaria Semolic ◽

Rocco Barazzoni

Keyword(s):

Oxidative Stress ◽

Fatty Acids ◽

Renal Failure ◽

Chronic Renal Failure ◽

Endothelial Dysfunction ◽

Polyunsaturated Fatty Acids ◽

Omega 3

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Absence of 12/15 Lipoxygenase Reduces Brain Oxidative Stress in Apolipoprotein E-Deficient Mice

American Journal Of Pathology ◽

10.1016/s0002-9440(10)61224-2 ◽

2005 ◽

Vol 167 (5) ◽

pp. 1371-1377 ◽

Cited By ~ 30

Author(s):

Cinzia M. Chinnici ◽

Yuemang Yao ◽

Tao Ding ◽

Colin D. Funk ◽

Domenico Praticò

Keyword(s):

Oxidative Stress ◽

Apolipoprotein E ◽

Brain Oxidative Stress ◽

Deficient Mice

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Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E–deficient mice

American Journal of Clinical Nutrition ◽

10.1093/ajcn/71.5.1062 ◽

2000 ◽

Vol 71 (5) ◽

pp. 1062-1076 ◽

Cited By ~ 473

Author(s):

Michael Aviram ◽

Leslie Dornfeld ◽

Mira Rosenblat ◽

Nina Volkova ◽

Marielle Kaplan ◽

...

Keyword(s):

Oxidative Stress ◽

Platelet Aggregation ◽

Apolipoprotein E ◽

Pomegranate Juice ◽

Deficient Mice

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Abstract 357: Hepatic ERK2 Suppresses Endoplasmic Reticulum Stress, Leading to Protection from Oxidative Stress and Endothelial Dysfunction

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.33.suppl_1.a357 ◽

2013 ◽

Vol 33 (suppl_1) ◽

Author(s):

Takehiko Kujiraoka ◽

Yasushi Satoh ◽

Makoto Ayaori ◽

Yasunaga Shiraishi ◽

Yuko Arai-Nakaya ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Endoplasmic Reticulum ◽

Fatty Acid ◽

Endothelial Dysfunction ◽

Er Stress ◽

Vascular Complications ◽

Metabolic Remodeling ◽

And Oxidative Stress

Background Insulin signaling comprises 2 major cascades, the IRS/PI3K/Akt and Ras/Raf/MEK/ERK pathways. Many studies on the tissue-specific effects of the former pathway had been conducted, however, the role of the latter cascade in tissue-specific insulin resistance had not been investigated. High glucose/fatty acid toxicity, inflammation and oxidative stress, all of which are associated with insulin resistance, can activate ERK. Liver plays a central role of metabolism and hepatosteatosis (HST) is associated with vascular diseases. The aim of this study is to elucidate the role of hepatic ERK2 in HST, metabolic remodeling and endothelial dysfunction. Methods Serum biomarkers of vascular complications in human were compared between subjects with and without HST diagnosed by echography for regular medical checkup. Next, we created liver-specific ERK2 knockout mice (LE2KO) and fed them with a high-fat/high-sucrose diet (HFHSD) for 20 weeks. The histological analysis, the expression of hepatic sarco/endoplasmic reticulum (ER) Ca 2+ -ATPase 2 (SERCA2) and glucose-tolerance/insulin-sensitivity (GT/IS) were tested. Vascular superoxide production and endothelial function were evaluated with dihydroethidium staining and isometric tension measurement of aorta. Results The presence of HST significantly increased HOMA-IR, an indicator of insulin resistance or atherosclerotic index in human. HFHSD-fed LE2KO revealed a marked exacerbation in HST and metabolic remodeling represented by the impairment of GT/IS, elevated serum free fatty acid and hyperhomocysteinemia without changes in body weight, blood pressure and serum cholesterol/triglyceride levels. In the HFHSD-fed LE2KO, mRNA and protein expressions of hepatic SERCA2 were significantly decreased, which resulted in hepatic ER stress. Induction of vascular superoxide production and remarkable endothelial dysfunction were also observed in them. Conclusions Hepatic ERK2 revealed the suppression of hepatic ER stress and HST in vivo , which resulted in protection from vascular oxidative stress and endothelial dysfunction. HST with hepatic ER stress can be a prominent risk of vascular complications by metabolic remodeling and oxidative stress in obese-related diseases.

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