The Role of the Nrf2/ARE Antioxidant System in Preventing Cardiovascular Diseases
Abstract
:1. Introduction
2. The Keap1-Nrf2-ARE Signaling System
2.1. Overview of Nrf2 Signaling
2.2. Effects on Mitochondria
2.3. AMPK Signaling
2.4. Notch Signaling
3. The Role of the Keap1-Nrf2-ARE Signaling System in Cardiovascular Diseases
3.1. Overview
3.2. Inflammation Is Misunderstood in the Past
3.3. Inflammation Is Important in CVD
3.4. The Keap1-Nrf2-ARE System Can Sense Shear Stress
3.5. The Nrf2 System Protects Mitochondria
3.6. Nrf2 Also Activates HO-1
3.7. Nrf2 Also Supports the ER
3.8. The Keap1-Nrf2-ARE Signaling System Is Important in Maintaining the Renewal of Cardiomyocytes
3.9. Nrf2 in Multi-Drug Resistant Cancer
4. Conclusions
Author Contributions
Conflicts of Interest
Abbreviations
AMP | Adenosine monophosphate |
AMPK | Adenosine monophosphate kinase |
ARE | Antioxidant response element |
ATP | Adenosine triphosphate |
βTrCP | β-transducin repeat containing protein |
CAPE | Caffeic acid phenethyl ester |
Cul3 | Cullin-3 based ligase |
CVD | Cardiovascular disease |
DJ-1 | Protein deglycase |
ECs | endothelial cells |
EGCG | Epigallocatechin-3-gallate |
ER | Endoplasmic reticulum |
GCL | Glutamate cysteine ligase |
GR | Glutathione reductase |
Grx | Glutaredoxin |
GSK-3 | Glycogen synthase kinase-3 |
GST | Glutathione S-transferase |
HDACs | histone deacetylases |
HO-1 | Heme oxygenase-1 |
Keap1 | Kelch-like enoyl-CoA hydratase-associated protein 1 |
Maf | Musculo-aponeurotic fibrosarcoma protein |
MAPK | mitogen-activated protein kinase |
miRNA | microRNA |
NAD(P)H | Nicotinamide adenine dinucleotide reduced form, with or without a phosphate |
NO | nitric oxide |
NQO1 | NAD(P)H:quinone oxidoreductase-1 |
Nrf2 | Nuclear erythroid-2 like factor-2 |
Nrf2+/+ | The wild type of Nrf2, in which both copies of the gene coding for Nrf2 are present |
Nrf2−/− | The genotype in which neither of the genes coding for Nrf2 are present |
OS | oscillatory disturbed shear |
p53 | A tumor suppressor protein with a molecular weight of 53 kiloDaltons |
PERK | Protein kinase RNA-like endoplasmic reticulum kinase |
PI3K | Phosphatidylinositol (3,4,5)-trisphosphate |
PKR | Protein kinase R |
PtdIns(3,4,5)-P3 | Phosphatidylinositol (3,4,5)-trisphosphate |
RNA | Ribonucleic acid |
ROS | Reactive oxygen species |
SOD | Superoxide dismutase |
SRC | Sarcoma |
SRXN | Sulfiredoxin |
TCDD | 2,3,7,8-tetrachlorodibenzodioxin |
TXN | Thioredoxin |
TXNRD | Thioredoxin reductase |
µM | micromoles per liter |
UPR | Unfolded protein response |
VCAM-1 | Vascular adhesion molecule-1 |
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Compound | Dietary Sources a | References |
---|---|---|
Epigallocatechin-3-gallate (EGCG) | Green tea | [11] |
Curcumin | Turmeric | [12] |
Carnosol | Rosemary | [12] |
Zerumbone | Ginger | [12] |
Caffeic acid phenethyl ester (CAPE) | Honeybee propolis and many plants | [12] |
Ethyl ferulate | Many plants, including eggplant | [12] |
Sulphorane | Broccoli and other cruciferous vegetables | [12] |
Resveratrol | Red wine, Itadori tea | [13] |
Quercetin | Many foods, including capers | [14] |
Cyanidin and cyanidin-3-O-glucoside | Many types of fruits and berries | [10] |
Catechin | Many foods, including cocoa and tea | [15] |
Epicatechin | Many foods, including cocoa and tea | [16] |
Kaempferol | Many foods, including green tea and berries | [16] |
Naringenin-7-O-glucoside | Many foods, including tomatoes | [16] |
Procyanidin B2 | Many foods, including cocoa and grape juice | [16] |
Genistein | Soybeans | [16] |
Butein and phloretin | Fruits, vegetables, nuts, tea, coffee, red wine | [16] |
Xanthohumol | Comon hop (Humulus lupulus) | [16] |
Luteolin | Many foods, including celery and broccoli | [17] |
Tangeretin | Tangerines and other citrus fruits | [17] |
Ellagic acid | Pomegranates | [18] |
Oleanolic acid | Many plants, including olive leaves | [19] |
Ganodermanondiol | Lingzhi mushrooms | [20] |
Echinatin | Licorice | [21] |
Chlorogenic acid | Green coffee extract, coffee | [22] |
N-methylpyridinium | Coffee | [22] |
Ursolic acid | Apple peels and many other foods and spices | [23] |
Hydroxytyrosol | Olive oil and olive leaves | [24] |
Rosmarinic acid | Rosemary | [25] |
Protocatechuic acid | Raspberries and many other foods | [26] |
Phloroglucinol aldehyde | Metabolite of anthocyanins | [27] |
p-coumaric acid | Many foods, including peanut and tomatoes | [28] |
Ferulic acid | Many herbs used in traditional Chinese medicine | [29] |
Isoorientin | Açaí, passion fruit, Sasa borealis | [16,30] |
Ascorbic acid | Vitamin C, citrus fruits | [31] |
Compound | Dietary Sources a | References |
---|---|---|
Ferulic acid | Many plant seeds and cell walls, including Ferula foetida | [30,55] |
Luteolin | Many foods, including celery and broccoli | [30,56] |
EGCG | Green tea and green tea extract | [30,57] |
Ascorbic acid | Vitamin C and citrus fruits | [30,58] |
Apigenin | Fruits, vegetables | [30,59] |
All-trans-retinoic acid | From β-carotene | [30,60] |
Brusatol | Brucea javanica | [30,61] |
Trigonelline | Fenugreek seeds | [30,62] |
Ochratoxin A | Aspergillus, Penicillum | [30,63] |
© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
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Smith, R.E.; Tran, K.; Smith, C.C.; McDonald, M.; Shejwalkar, P.; Hara, K. The Role of the Nrf2/ARE Antioxidant System in Preventing Cardiovascular Diseases. Diseases 2016, 4, 34. https://doi.org/10.3390/diseases4040034
Smith RE, Tran K, Smith CC, McDonald M, Shejwalkar P, Hara K. The Role of the Nrf2/ARE Antioxidant System in Preventing Cardiovascular Diseases. Diseases. 2016; 4(4):34. https://doi.org/10.3390/diseases4040034
Chicago/Turabian StyleSmith, Robert E., Kevin Tran, Cynthia C. Smith, Miranda McDonald, Pushkar Shejwalkar, and Kenji Hara. 2016. "The Role of the Nrf2/ARE Antioxidant System in Preventing Cardiovascular Diseases" Diseases 4, no. 4: 34. https://doi.org/10.3390/diseases4040034