Reactive Oxygen Species and Pulmonary Vasculature During Hypobaric Hypoxia DOI Creative Commons
Patricia Siqués, Julio Brito, Eduardo Pena

et al.

Frontiers in Physiology, Journal Year: 2018, Volume and Issue: 9

Published: July 9, 2018

An increasing number of people are living or working at high altitudes (hypobaric hypoxia) and therefore suffering several physiological, biochemical molecular changes. Pulmonary vasculature is one the main first responses to hypoxia. These imply hypoxic pulmonary vasoconstriction (HPV), remodeling eventually hypertension. events occur according type extension exposure. There also evidence that these changes in vascular bed could be mainly attributed a homeostatic imbalance as result increased levels reactive oxygen species (ROS). The increase ROS production during hypobaric hypoxia has been an enhanced activity expression nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase), though there some dispute about which subunit involved. This enzymatic complex may directly induced by hypoxia-inducible factor-1α (HIF1-α). found related pathways, cells, enzymes molecules responses, from inflammation, structural changes, such and, ultimately, Therefore, we performed comprehensive review current on role development under conditions, with focus provides information supporting oxidative stress (mainly ROS) vasculature´s depicting possible future therapeutics research targets. NADPH oxidase-produced highlighted major source ROS. Moreover, new molecules, ADMA, critical inflammatory cells fibroblasts, Several controversies remain regarding mechanisms involved need elucidated.

Language: Английский

Complex interplay between autophagy and oxidative stress in the development of pulmonary disease DOI Creative Commons
Wojciech Ornatowski, Qing Lü, Manivannan Yegambaram

et al.

Redox Biology, Journal Year: 2020, Volume and Issue: 36, P. 101679 - 101679

Published: Aug. 11, 2020

The autophagic pathway involves the encapsulation of substrates in double-membraned vesicles, which are subsequently delivered to lysosome for enzymatic degradation and recycling metabolic precursors. Autophagy is a major cellular defense against oxidative stress, or related conditions that cause accumulation damaged proteins organelles. Selective forms autophagy can maintain organelle populations remove aggregated proteins. Dysregulation redox homeostasis under pathological results excessive generation reactive oxygen species (ROS), leading stress associated damage components. Accumulating evidence indicates necessary homeostasis. ROS activates autophagy, facilitates adaptation diminishes by degrading intracellular macromolecules dysfunctional responses triggered include altered regulation signaling pathways culminate autophagy. Current research suggests central role as mammalian response its interrelationship other systems. Altered phenotypes have been observed lung diseases such chronic obstructive disease, acute injury, cystic fibrosis, idiopathic pulmonary arterial hypertension, asthma. Understanding mechanisms regulate will provide novel therapeutic targets diseases. This review highlights our current understanding on interplay between development disease.

Language: Английский

Citations

304
The role of inflammation in hypoxic pulmonary hypertension: from cellular mechanisms to clinical phenotypes DOI
Steven C. Pugliese, Jens M. Poth,

Mehdi A. Fini

et al.

AJP Lung Cellular and Molecular Physiology, Journal Year: 2014, Volume and Issue: 308(3), P. L229 - L252

Published: Nov. 22, 2014

Hypoxic pulmonary hypertension (PH) comprises a heterogeneous group of diseases sharing the common feature chronic hypoxia-induced vascular remodeling. The disease is usually characterized by mild to moderate remodeling that largely thought be reversible compared with progressive irreversible seen in World Health Organization (WHO) I disease. However, these patients, presence PH significantly worsens morbidity and mortality. In addition, small subset patients hypoxic develop "out-of-proportion" severe similar WHO all cases hypoxia-related PH, inflammation, particularly persistent play role. This review focuses on effects hypoxia cells signaling pathways involved initiation perpetuation especially as they relate transition PH. We hypothesize combination local tissue factors/cytokines ("second hit") antagonizes homeostatic cellular interactions between mesenchymal (fibroblasts and/or smooth muscle cells) macrophages arrests an epigenetically locked permanently activated proremodeling proinflammatory phenotype. aberrant cross-talk promotes nonresolving inflammation remodeling, perpetuating A better understanding may lead development specific therapeutic targets, none are currently available for III

Language: Английский

Citations

190
Alginate derived functional oligosaccharides: Recent developments, barriers, and future outlooks DOI
Ushasree Mrudulakumari Vasudevan,

Ok Kyung Lee,

Eun Yeol Lee

et al.

Carbohydrate Polymers, Journal Year: 2021, Volume and Issue: 267, P. 118158 - 118158

Published: May 7, 2021

Language: Английский

Citations

105
Gestational Hypoxia and Developmental Plasticity DOI Open Access

Charles A. Ducsay,

Ravi Goyal, William J. Pearce

et al.

Physiological Reviews, Journal Year: 2018, Volume and Issue: 98(3), P. 1241 - 1334

Published: May 2, 2018

Hypoxia is one of the most common and severe challenges to maintenance homeostasis. Oxygen sensing a property all tissues, response hypoxia multidimensional involving complicated intracellular networks concerned with transduction hypoxia-induced responses. Of stresses which fetus newborn infant are subjected, perhaps important clinically relevant that hypoxia. during gestation impacts both mother fetal development through interactions an individual's genetic traits acquired over multiple generations by natural selection changes in gene expression patterns altering epigenetic code. Changes epigenome determine "genomic plasticity," i.e., ability genes be differentially expressed according environmental cues. The genomic plasticity defined epigenomic mechanisms including DNA methylation, histone modifications, noncoding RNAs mechanistic substrate for phenotypic programming determines physiological risk healthy or deleterious outcomes. This review explores impact gestational on maternal health development, developmental emphasis uteroplacental circulation, heart cerebral pulmonary hypothalamic-pituitary-adrenal axis adipose tissue. complex molecular may physiology disease later life discussed.

Language: Английский

Citations

161
NADPH oxidases and vascular remodeling in cardiovascular diseases DOI
Ana B. García‐Redondo, Andrea Aguado, Ana M. Briones

et al.

Pharmacological Research, Journal Year: 2016, Volume and Issue: 114, P. 110 - 120

Published: Oct. 20, 2016

Language: Английский

Citations

128
DNA Damage and Pulmonary Hypertension DOI Open Access
Benoît Ranchoux, Jolyane Meloche, Roxane Paulin

et al.

International Journal of Molecular Sciences, Journal Year: 2016, Volume and Issue: 17(6), P. 990 - 990

Published: June 22, 2016

Pulmonary hypertension (PH) is defined by a mean pulmonary arterial pressure over 25 mmHg at rest and diagnosed right heart catheterization. Among the different groups of PH, (PAH) characterized progressive obstruction distal arteries, related to endothelial cell dysfunction vascular proliferation, which leads an increased resistance, ventricular hypertrophy, failure. Although primary trigger PAH remains unknown, oxidative stress inflammation have been shown play key role in development progression remodeling. These factors are known increase DNA damage that might favor emergence proliferative apoptosis-resistant phenotype observed cells. High levels were reported occur lungs remodeled arteries as well animal models PH. Moreover, recent studies demonstrated impaired DNA-response mechanisms may lead mutagen sensitivity patients. Finally, was linked with decreased breast cancer 1 protein (BRCA1) topoisomerase 2-binding (TopBP1) expression, both involved maintaining genome integrity. This review aims provide overview evidence repair deficiency their implication pathogenesis.

Language: Английский

Citations

98
NADPH oxidase in the vasculature: Expression, regulation and signalling pathways; role in normal cardiovascular physiology and its dysregulation in hypertension DOI
Greg A. Knock

Free Radical Biology and Medicine, Journal Year: 2019, Volume and Issue: 145, P. 385 - 427

Published: Oct. 1, 2019

Language: Английский

Citations

93
Obesity, estrogens and adipose tissue dysfunction – implications for pulmonary arterial hypertension DOI Creative Commons

Kirsty M. Mair,

Rosemary Gaw,

Margaret R. MacLean

et al.

Pulmonary Circulation, Journal Year: 2020, Volume and Issue: 10(3), P. 1 - 21

Published: July 1, 2020

Obesity is a prevalent global public health issue characterized by excess body fat. Adipose tissue now recognized as an important endocrine organ releasing abundance of bioactive adipokines including, but not limited to, leptin, adiponectin and resistin. common comorbidity amongst pulmonary arterial hypertension patients, with 30% to 40% reported obese, independent other comorbidities associated (e.g. obstructive sleep apnoea). An 'obesity paradox' has been observed, where obesity subclinical right ventricular dysfunction paradoxically may confer protective effect on function once develops. share multiple pathophysiological mechanisms including inflammation, oxidative stress, elevated leptin (proinflammatory) reduced (anti-inflammatory). The female prevalence instigated the hypothesis that estrogens play causative role in its development. tissue, major site for storage metabolism sex steroids, primary source circulating levels which are postmenopausal women men hypertension. This review discusses functions adipose both links between Shared contribution specific fat depots, metabolic sex-dependent differences discussed.

Language: Английский

Citations

88
Autophagy-modulating biomaterials: multifunctional weapons to promote tissue regeneration DOI Creative Commons
Yan Wu, Luxin Li,

Zuojun Ning

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 15, 2024

Autophagy is a self-renewal mechanism that maintains homeostasis and can promote tissue regeneration by regulating inflammation, reducing oxidative stress promoting cell differentiation. The interaction between biomaterials cells significantly affects biomaterial-tissue integration regeneration. In recent years, it has been found affect various processes related to autophagy. utilization of in controlled environment become prominent approach for enhancing the capabilities. This involves regulation autophagy diverse types implicated regeneration, encompassing modulation inflammatory responses, stress, differentiation, proliferation, migration, apoptosis, extracellular matrix formation. addition, possess potential serve as carriers drug delivery, enabling either activating or inhibiting its processes. review summarizes relationship discusses role biomaterial-based advanced technologies used design autophagy-modulating are summarized, rational providing via modification chemistry surface incorporation molecules discussed. A better understanding well underlying molecular mechanisms, may lead new possibilities Video Abstract.

Language: Английский

Citations

9
Dysfunction in mitochondrial electron transport chain drives the pathogenesis of pulmonary arterial hypertension: insights from a multi-omics investigation DOI Creative Commons
Xin Zhang, Jieling Li, Minyi Fu

et al.

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 20, 2025

Pulmonary arterial hypertension (PAH) is a progressive disorder that can lead to right ventricular failure and severe consequences. Despite extensive efforts, limited progress has been made in preventing the progression of PAH. Mitochondrial dysfunction implicated development PAH, but key mitochondrial functional alterations pathogenesis have yet be elucidated. We integrated three microarray datasets from Gene Expression Omnibus (GEO), including 222 lung samples (164 58 controls), for differential expression enrichment analyses. Machine learning identified mitochondria-related signaling pathways. PAH control tissue were collected, transcriptomic metabolomic profiling performed. Kyoto Encyclopedia Genes Genomes (KEGG) analysis investigated shared pathways, canonical correlation assessed gene-metabolite relationships. In GEO datasets, pathways significantly enriched samples, particular electron transport chain (ETC) oxidative phosphorylation system. Notably, cytochrome c oxygen ETC was as most crucial pathway, which down-regulated samples. Transcriptomic clinical 14 differentially expressed genes (DEGs) related function. Metabolomic revealed metabolites samples: increased 3-phenyllactic acid ADP, decreased citric acid. Mitochondria-related highly correlated with these included KIT, OTC, CAMK2A, CHRNA1. Down-regulation disruption cycle homeostasis may contribute pathogenesis. emerges potential novel diagnostic biomarker These findings offer insights developing therapies diagnostics.

Language: Английский

Citations

1