Reactive Oxygen Species in Pulmonary Vascular Remodeling DOI
Saurabh Aggarwal, Christine Groß, Shruti Sharma

et al.

Comprehensive physiology, Journal Year: 2013, Volume and Issue: unknown, P. 1011 - 1034

Published: July 1, 2013

The pathogenesis of pulmonary hypertension is a complex multifactorial process that involves the remodeling arteries. This encompasses concentric medial thickening small arterioles, neomuscularization previously nonmuscular capillary-like vessels, and structural wall changes in larger arterial muscularization characterized by vascular smooth muscle cell hyperplasia hypertrophy. In addition, uncontrolled hypertension, clonal expansion apoptosis-resistant endothelial cells leads to formation plexiform lesions. Based upon large number studies animal models, three major stimuli drive are inflammation, shear stress, hypoxia. Although, precise mechanisms which these impair function structure unknown, reactive oxygen species (ROS)-mediated oxidative damage appears play an important role. ROS highly due their unpaired valence shell electron. Oxidative occurs when production exceeds quenching capacity antioxidant cell. can be produced from complexes membrane (nicotinamide adenine dinucleotide phosphate-oxidase), cellular organelles (peroxisomes mitochondria), cytoplasm (xanthine oxidase). Furthermore, low levels tetrahydrobiopterin (BH4) L-arginine rate limiting cofactor substrate for nitric oxide synthase (eNOS), cause uncoupling eNOS, resulting decreased NO increased production. review will focus on generation systems, scavenger antioxidants, stress associated alterations hypertension. © 2013 American Physiological Society. Compr Physiol 3:1011-1034, 2013.

Language: Английский

Hypoxic Pulmonary Vasoconstriction DOI
Kimberly J. Dunham‐Snary, Danchen Wu,

Edward A. Sykes

et al.

CHEST Journal, Journal Year: 2016, Volume and Issue: 151(1), P. 181 - 192

Published: Sept. 17, 2016

Language: Английский

Citations

390

Pulmonary Vascular Hemodynamic Response to Exercise in Cardiopulmonary Diseases DOI Open Access
Gregory D. Lewis, Eduardo Bossone, Robert Naeije

et al.

Circulation, Journal Year: 2013, Volume and Issue: 128(13), P. 1470 - 1479

Published: Sept. 23, 2013

Language: Английский

Citations

349

Perinuclear Mitochondrial Clustering Creates an Oxidant-Rich Nuclear Domain Required for Hypoxia-Induced Transcription DOI

Abu‐Bakr Al‐Mehdi,

Viktor M. Pastukh,

Brad M. Swiger

et al.

Science Signaling, Journal Year: 2012, Volume and Issue: 5(231)

Published: July 3, 2012

Reactive oxygen species generated by mitochondria that redistribute near the nucleus promote transcriptional responses to hypoxia.

Language: Английский

Citations

343

Lung Injury After One-Lung Ventilation DOI Open Access
Jens Lohser, Peter Slinger

Anesthesia & Analgesia, Journal Year: 2015, Volume and Issue: 121(2), P. 302 - 318

Published: July 22, 2015

Lung injury is the leading cause of death after thoracic surgery. Initially recognized pneumonectomy, it has since been described any period 1-lung ventilation (OLV), even in absence lung resection. Overhydration and high tidal volumes were thought to be responsible at various points; however, now that pathophysiology more complex multifactorial. All causative mechanisms known trigger ventilator-induced have OLV setting. The ventilated exposed strain secondary large, nonphysiologic loss normal functional residual capacity. In addition, experiences oxidative stress, as well capillary shear stress because hyperperfusion. Surgical manipulation and/or resection collapsed may induce injury. Re-expansion conclusion invariably induces duration-dependent, ischemia-reperfusion Inflammatory cytokines are released response localized promote local contralateral Protective volatile anesthesia lessen degree injury; increases biochemical histologic markers appear unavoidable. endothelial glycocalyx represent a common pathway for creation during OLV, damaged by most injurious mechanisms. Experimental therapies stabilize afford ability reduce future. interim, protective with 4 5 mL/kg predicted body weight, positive end-expiratory pressure 10 cm H2O, routine recruitment should used an attempt minimize harmful strain. Additional strategies include efforts duration hyperoxia.

Language: Английский

Citations

340

Superoxide generation by complex III: From mechanistic rationales to functional consequences DOI Creative Commons

Lea Bleier,

Stefan Dröse

Biochimica et Biophysica Acta (BBA) - Bioenergetics, Journal Year: 2012, Volume and Issue: 1827(11-12), P. 1320 - 1331

Published: Dec. 23, 2012

Apart from complex I (NADH:ubiquinone oxidoreductase) the mitochondrial cytochrome bc1 (complex III; ubiquinol:cytochrome c has been identified as main producer of superoxide and derived reactive oxygen species (ROS) within respiratory chain. Mitochondrial ROS are generally linked to oxidative stress, aging other pathophysiological settings like in neurodegenerative diseases. However, produced at ubiquinol oxidation center (center P, Qo site) III seem have additional physiological functions signaling molecules during cellular processes adaptation hypoxia. The molecular mechanism production that is mechanistically electron bifurcation still a matter debate. Some insight comes extensive kinetic studies with mutated complexes yeast bacterial complexes. This review intended bridge gap between those mechanistic investigations on signal transduction highlights factors impact generation. article part Special Issue entitled: Respiratory related bc

Language: Английский

Citations

333

Gas exchange and ventilation–perfusion relationships in the lung DOI Open Access
Johan Petersson, Robb W. Glenny

European Respiratory Journal, Journal Year: 2014, Volume and Issue: 44(4), P. 1023 - 1041

Published: July 25, 2014

This review provides an overview of the relationship between ventilation/perfusion ratios and gas exchange in lung, emphasising basic concepts relating them to clinical scenarios. For each exchanging unit, alveolar effluent blood partial pressures oxygen carbon dioxide ( P O 2 CO ) are determined by ratio ventilation flow V ′ A /Q ′) for unit. Shunt low regions two examples mismatch most frequent causes hypoxaemia. Diffusion limitation, hypoventilation inspired cause hypoxaemia, even absence mismatch. In contrast other causes, hypoxaemia due shunt responds poorly supplemental oxygen. Gas units with little or no (high regions) result dead space increased wasted ventilation, i.e. less efficient removal. Because respiratory drive maintain a normal arterial , is minute work breathing, not hypercapnia. Calculations alveolar–arterial tension difference, venous admixture provide quantitative estimates effect on exchange. The types causing impaired vary characteristically different lung diseases.

Language: Английский

Citations

315

Defining Physiological Normoxia for Improved Translation of Cell Physiology to Animal Models and Humans DOI Open Access
Thomas P. Keeley, Giovanni E. Mann

Physiological Reviews, Journal Year: 2018, Volume and Issue: 99(1), P. 161 - 234

Published: Oct. 24, 2018

The extensive oxygen gradient between the air we breathe (Po2 ~21 kPa) and its ultimate distribution within mitochondria (as low as ~0.5-1 is testament to efforts expended in limiting inherent toxicity. It has long been recognized that cell culture undertaken under room conditions falls short of replicating this protection vitro. Despite this, difficulty accurately determining appropriate O2 levels which cells, coupled with a lack technology replicate maintain physiological environment vitro, hindered addressing issue thus far. In review, aim address current understanding tissue Po2 vivo summarize attempts made these state-of-the-art techniques employed determine levels, well issues associated reproducing are also critically reviewed. We provide framework for researchers undertake relevant specific tissues organs. envisage review will facilitate paradigm shift, enabling translation findings vitro disease pathology design novel therapeutics.

Language: Английский

Citations

267

Pulmonary vascular remodeling in pulmonary hypertension DOI
Rubin M. Tuder

Cell and Tissue Research, Journal Year: 2016, Volume and Issue: 367(3), P. 643 - 649

Published: Dec. 26, 2016

Language: Английский

Citations

264

Hypoxic Pulmonary Vasoconstriction DOI Open Access
Andrew B Lumb, Peter Slinger

Anesthesiology, Journal Year: 2015, Volume and Issue: 122(4), P. 932 - 946

Published: Jan. 14, 2015

Hypoxic pulmonary vasoconstriction (HPV) represents a fundamental difference between the and systemic circulations. HPV is active in utero, reducing blood flow, adults helps to match regional ventilation perfusion although it has little effect healthy lungs. Many factors affect including pH or PCO2, cardiac output, several drugs, antihypertensives. In patients with lung pathology any patient having one-lung ventilation, contributes maintaining oxygenation, so anesthesiologists should be aware of effects anesthesia on this protective reflex. Intravenous anesthetic drugs have HPV, but attenuated by inhaled anesthetics, less newer agents. The reflex biphasic, once second phase becomes after about an hour hypoxia, takes hours reverse when normoxia returns. This significant clinical implications for repeated periods ventilation.

Language: Английский

Citations

263

Metabolism of vascular smooth muscle cells in vascular diseases DOI Open Access
Jia Shi, Yi Yang,

Anying Cheng

et al.

AJP Heart and Circulatory Physiology, Journal Year: 2020, Volume and Issue: 319(3), P. H613 - H631

Published: Aug. 7, 2020

Vascular smooth muscle cells (VSMCs) are the fundamental component of medial layer arteries and essential for arterial physiology pathology. It is becoming increasingly clear that VSMCs can alter their metabolism to fulfill bioenergetic biosynthetic requirements. During vascular injury, switch from a quiescent “contractile” phenotype highly migratory proliferative “synthetic” phenotype. Recent studies have found switching driven by metabolic switch. Metabolic pathways, including aerobic glycolysis, fatty acid oxidation, amino metabolism, distinct, indispensable roles in normal dysfunctional vasculature. also related endothelial cells. In present review, we brief overview how it regulates progression several diseases, atherosclerosis, systemic hypertension, diabetes, pulmonary calcification, aneurysms, effect risk factors disease (aging, cigarette smoking, excessive alcohol drinking) on VSMC clarify role key pathological process.

Language: Английский

Citations

250