Updated Role of Neuropeptide Y in Nicotine-Induced Endothelial Dysfunction and Atherosclerosis

Cardiovascular disease is the leading cause of death worldwide. Endothelial dysfunction of the arterial vasculature plays a pivotal role in cardiovascular pathogenesis. Nicotine-induced endothelial dysfunction substantially contributes to the development of arteriosclerotic cardiovascular disease. Nicotine promotes oxidative inflammation, thrombosis, pathological angiogenesis, and vasoconstriction, and induces insulin resistance. However, the exact mechanism through which nicotine induces endothelial dysfunction remains unclear. Neuropeptide Y (NPY) is widely distributed in the central nervous system and peripheral tissues, and it participates in the pathogenesis of atherosclerosis by regulating vasoconstriction, energy metabolism, local plaque inflammatory response, activation and aggregation of platelets, and stress and anxiety-related emotion. Nicotine can increase the expression of NPY, suggesting that NPY is involved in nicotine-induced endothelial dysfunction. Herein, we present an updated review of the possible mechanisms of nicotine-induced atherosclerosis, with a focus on endothelial cell dysfunction associated with nicotine and NPY.

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The Role of Neuropeptide Y and Peptide YY in the Development of Obesity via Gut-brain Axis

Current Protein and Peptide Science ◽

10.2174/1389203720666190125105401 ◽

2019 ◽

Vol 20 (7) ◽

pp. 750-758 ◽

Cited By ~ 7

Author(s):

Yi Wu ◽

Hengxun He ◽

Zhibin Cheng ◽

Yueyu Bai ◽

Xi Ma

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neuropeptide Y ◽

Metabolic Diseases ◽

Peptide Yy ◽

Vital Role ◽

Gut Peptides ◽

Nonalcoholic Fatty Liver ◽

The Central Nervous System

Obesity is one of the main challenges of public health in the 21st century. Obesity can induce a series of chronic metabolic diseases, such as diabetes, dyslipidemia, hypertension and nonalcoholic fatty liver, which seriously affect human health. Gut-brain axis, the two-direction pathway formed between enteric nervous system and central nervous system, plays a vital role in the occurrence and development of obesity. Gastrointestinal signals are projected through the gut-brain axis to nervous system, and respond to various gastrointestinal stimulation. The central nervous system regulates visceral activity through the gut-brain axis. Brain-gut peptides have important regulatory roles in the gut-brain axis. The brain-gut peptides of the gastrointestinal system and the nervous system regulate the gastrointestinal movement, feeling, secretion, absorption and other complex functions through endocrine, neurosecretion and paracrine to secrete peptides. Both neuropeptide Y and peptide YY belong to the pancreatic polypeptide family and are important brain-gut peptides. Neuropeptide Y and peptide YY have functions that are closely related to appetite regulation and obesity formation. This review describes the role of the gutbrain axis in regulating appetite and maintaining energy balance, and the functions of brain-gut peptides neuropeptide Y and peptide YY in obesity. The relationship between NPY and PYY and the interaction between the NPY-PYY signaling with the gut microbiota are also described in this review.

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The Role of Asymmetric Dimethylarginine (ADMA) in Endothelial Dysfunction and Cardiovascular Disease

Current Cardiology Reviews ◽

10.2174/1573210ccr06210403x ◽

2010 ◽

Vol 999 (999) ◽

pp. 1-8

Author(s):

Latika Sibal

Keyword(s):

Cardiovascular Disease ◽

Endothelial Dysfunction ◽

Asymmetric Dimethylarginine

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Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

Journal of Endocrinology ◽

10.1530/joe-16-0340 ◽

2017 ◽

Vol 232 (1) ◽

pp. R27-R44 ◽

Cited By ~ 90

Author(s):

D S Boeldt ◽

I M Bird

Keyword(s):

Endothelial Cell ◽

Endothelial Dysfunction ◽

Cell Function ◽

Endothelial Cell Dysfunction ◽

Hypertensive Disorders Of Pregnancy ◽

Endothelial Cell Function ◽

Vascular Adaptation ◽

Cell Dysfunction ◽

Maternal Adaptation ◽

Flow Through

Maternal vascular adaptation to pregnancy is critically important to expand the capacity for blood flow through the uteroplacental unit to meet the needs of the developing fetus. Failure of the maternal vasculature to properly adapt can result in hypertensive disorders of pregnancy such as preeclampsia (PE). Herein, we review the endocrinology of maternal adaptation to pregnancy and contrast this with that of PE. Our focus is specifically on those hormones that directly influence endothelial cell function and dysfunction, as endothelial cell dysfunction is a hallmark of PE. A variety of growth factors and cytokines are present in normal vascular adaptation to pregnancy. However, they have also been shown to be circulating at abnormal levels in PE pregnancies. Many of these factors promote endothelial dysfunction when present at abnormal levels by acutely inhibiting key Ca2+ signaling events and chronically promoting the breakdown of endothelial cell–cell contacts. Increasingly, our understanding of how the contributions of the placenta, immune cells, and the endothelium itself promote the endocrine milieu of PE is becoming clearer. We then describe in detail how the complex endocrine environment of PE affects endothelial cell function, why this has contributed to the difficulty in fully understanding and treating this disorder, and how a focus on signaling convergence points of many hormones may be a more successful treatment strategy.

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Role of glutathione redox cycle in TNF-α-mediated endothelial cell dysfunction

Atherosclerosis ◽

10.1016/0021-9150(95)05568-h ◽

1995 ◽

Vol 117 (2) ◽

pp. 179-188 ◽

Cited By ~ 43

Author(s):

Michal Toborek ◽

Steven W. Barger ◽

Mark P. Mattson ◽

Craig J. McClain ◽

Bernhard Hennig

Keyword(s):

Endothelial Cell ◽

Redox Cycle ◽

Endothelial Cell Dysfunction ◽

Cell Dysfunction ◽

Glutathione Redox Cycle ◽

Tnf Α ◽

Glutathione Redox

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A Critique of Aspects of Methodological Approaches to the Role of the Central Nervous System in Cardiovascular Disease

Psychosomatic Medicine ◽

10.1097/00006842-196407000-00022 ◽

1964 ◽

Vol 26 (4) ◽

pp. 432-453

Author(s):

&NA; &NA;

Keyword(s):

Cardiovascular Disease ◽

Central Nervous System ◽

Nervous System ◽

The Central Nervous System ◽

Methodological Approaches

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Role of Endothelial Dysfunction in Cardiovascular Disease: A Review

Journal of Health and Translational Medicine ◽

10.22452/jummec.vol5no2.2 ◽

2000 ◽

Vol 5 (2) ◽

pp. 59-66

Author(s):

Amudha Kadirvelu ◽

Chee Kok Han ◽

Tan Kim Heung ◽

Anna Maria Choy ◽

Mustafa Mohd Rais ◽

...

Keyword(s):

Cardiovascular Disease ◽

Endothelial Dysfunction

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Epigenetic Regulation of Endothelial Dysfunction and Inflammation in Pulmonary Arterial Hypertension

International Journal of Molecular Sciences ◽

10.3390/ijms222212098 ◽

2021 ◽

Vol 22 (22) ◽

pp. 12098

Author(s):

Jaylen Hudson ◽

Laszlo Farkas

Keyword(s):

Endothelial Dysfunction ◽

Pulmonary Artery Hypertension ◽

Metabolic Reprogramming ◽

Pulmonary Vascular Disease ◽

Epigenetic Changes ◽

Apoptosis Resistance ◽

Cell Dysfunction ◽

Pulmonary Arterial ◽

Non Coding Rnas

Once perceived as a disorder treated by vasodilation, pulmonary artery hypertension (PAH) has emerged as a pulmonary vascular disease with severe endothelial cell dysfunction. In the absence of a cure, many studies seek to understand the detailed mechanisms of EC regulation to potentially create more therapeutic options for PAH. Endothelial dysfunction is characterized by complex phenotypic changes including unchecked proliferation, apoptosis-resistance, enhanced inflammatory signaling and metabolic reprogramming. Recent studies have highlighted the role of epigenetic modifications leading to pro-inflammatory response pathways, endothelial dysfunction, and the progression of PAH. This review summarizes the existing literature on epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs, which can lead to aberrant endothelial function. Our goal is to develop a conceptual framework for immune dysregulation and epigenetic changes in endothelial cells in the context of PAH. These studies as well as others may lead to advances in therapeutics to treat this devastating disease.

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Methylglyoxal triggers human aortic endothelial cell dysfunction via modulation of the KATP/MAPK pathway

AJP Cell Physiology ◽

10.1152/ajpcell.00117.2018 ◽

2019 ◽

Vol 317 (1) ◽

pp. C68-C81 ◽

Cited By ~ 3

Author(s):

Yihan Wang ◽

Leo M. Hall ◽

Marisa Kujawa ◽

Hainan Li ◽

Xiang Zhang ◽

...

Keyword(s):

Endothelial Cell ◽

Endothelial Dysfunction ◽

Network Formation ◽

Cell Function ◽

Mapk Pathway ◽

Endothelial Cell Dysfunction ◽

Endothelial Cell Function ◽

Cell Dysfunction ◽

Type 2 Diabetic

Endothelial dysfunction is a key risk factor in diabetes-related multiorgan damage. Methylglyoxal (MGO), a highly reactive dicarbonyl generated primarily as a by-product of glycolysis, is increased in both type 1 and type 2 diabetic patients. MGO can rapidly bind with proteins, nucleic acids, and lipids, resulting in structural and functional changes. MGO can also form advanced glycation end products (AGEs). How MGO causes endothelial cell dysfunction, however, is not clear. Human aortic endothelial cells (HAECs) from healthy (H-HAECs) and type 2 diabetic (D-HAECs) donors were cultured in endothelial growth medium (EGM-2). D-HAECs demonstrated impaired network formation (on Matrigel) and proliferation (MTT assay), as well as increased apoptosis (caspase-3/7 activity and TUNEL staining), compared with H-HAECs. High glucose (25 mM) or AGEs (200 ng/ml) did not induce such immediate, detrimental effects as MGO (10 µM). H-HAECs were treated with MGO (10 µM) for 24 h with or without the ATP-sensitive potassium (KATP) channel antagonist glibenclamide (1 µM). MGO significantly impaired H-HAEC network formation and proliferation and induced cell apoptosis, which was reversed by glibenclamide. Furthermore, siRNA against the KATP channel protein Kir6.1 significantly inhibited endothelial cell function at basal status but rescued impaired endothelial cell function upon MGO exposure. Meanwhile, activation of MAPK pathways p38 kinase, c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) (determined by Western blot analyses of their phosphorylated forms, p-JNK, p-p38, and p-ERK) in D-HAECs were significantly enhanced compared with those in H-HAECs. MGO exposure enhanced the activation of all three MAPK pathways in H-HAECs, whereas glibenclamide reversed the activation of p-stress-activated protein kinase/JNK induced by MGO. Glyoxalase-1 (GLO1) is the endogenous MGO-detoxifying enzyme. In healthy mice that received an inhibitor of GLO1, MGO deposition in aortic wall was enhanced and endothelial cell sprouting from isolated aortic segment was significantly inhibited. Our data suggest that MGO triggers endothelial cell dysfunction by activating the JNK/p38 MAPK pathway. This effect arises partly through activation of KATP channels. By understanding how MGO induces endothelial dysfunction, our study may provide useful information for developing MGO-targeted interventions to treat vascular disorders in diabetes.

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Endoplasmic Reticulum Stress: A Critical Molecular Driver of Endothelial Dysfunction and Cardiovascular Disturbances Associated with Diabetes

International Journal of Molecular Sciences ◽

10.3390/ijms20071658 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1658 ◽

Cited By ~ 29

Author(s):

Hatem Maamoun ◽

Shahenda Abdelsalam ◽

Asad Zeidan ◽

Hesham Korashy ◽

Abdelali Agouni

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Cardiovascular Disease ◽

Endoplasmic Reticulum ◽

Endothelial Cell ◽

Er Stress ◽

Cardiovascular Complications ◽

Endothelial Cell Dysfunction ◽

Cell Dysfunction ◽

Obesity And Diabetes

Physical inactivity and sedentary lifestyle contribute to the widespread epidemic of obesity among both adults and children leading to rising cases of diabetes. Cardiovascular disease complications associated with obesity and diabetes are closely linked to insulin resistance and its complex implications on vascular cells particularly endothelial cells. Endoplasmic reticulum (ER) stress is activated following disruption in post-translational protein folding and maturation within the ER in metabolic conditions characterized by heavy demand on protein synthesis, such as obesity and diabetes. ER stress has gained much interest as a key bridging and converging molecular link between insulin resistance, oxidative stress, and endothelial cell dysfunction and, hence, represents an interesting drug target for diabetes and its cardiovascular complications. We reviewed here the role of ER stress in endothelial cell dysfunction, the primary step in the onset of atherosclerosis and cardiovascular disease. We specifically focused on the contribution of oxidative stress, insulin resistance, endothelial cell death, and cellular inflammation caused by ER stress in endothelial cell dysfunction and the process of atherogenesis.

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