Vascular remodeling in the circulations of the lung

2004 ◽  
Vol 97 (5) ◽  
pp. 1999-2004 ◽  
Author(s):  
Wayne Mitzner ◽  
Elizabeth M. Wagner
Keyword(s):  
Pulmonary Circulation ◽  
Vascular Remodeling ◽  
Pulmonary Arteries ◽  
Future Research ◽  
Striking Difference ◽  
The Novel ◽  
Molecular Signaling ◽  
Bronchial Arteries ◽  
Bronchial Circulation ◽  
Systemic Arteries

The lung is unique in its double sources of perfusion from the pulmonary and systemic circulations. One striking difference between the two circulations is the capacity for angiogenesis. The bronchial circulation has a capacity that seems quite similar to all systemic arteries, whereas the pulmonary circulation seems relatively inert in this regard. Extra-alveolar pulmonary arteries can grow somewhat in length, and septal capillaries seem to have the capability of reforming, but these processes do not seem to occur with nearly the same intensity associated with the bronchial arteries. In this review, we emphasize these differences between the two circulations of the lung, anticipating that future research will allow more focused probing into the molecular signaling that regulates the novel mechanistic and pathological pathways of each.

scholarly journals A STUDY OF THE RELATION OF PULMONARY AND BRONCHIAL CIRCULATION

1913 ◽  
Vol 18 (5) ◽  
pp. 500-506 ◽  
Author(s):  
Albert A. Ghoreyeb ◽  
Howard T. Karsner
Keyword(s):  
Pulmonary Artery ◽  
Lung Tissue ◽  
Bronchial Artery ◽  
Venous Blood ◽  
Pulmonary Arteries ◽  
The Other ◽  
Main Trunk ◽  
Intimate Contact ◽  
Bronchial Arteries ◽  
Bronchial Circulation

The most striking point brought out in this study is that as long as a definite pressure is maintained in either the pulmonary or bronchial circulations, the admixture of bloods is extremely limited. It is easily conceivable that more mixture occurs normally than under the conditions of the experiment, but there is no reason for considering this to be a large difference. If, however, in either system the pressure sinks to zero the possibility of supply by the other system becomes evident. It takes much longer for the mass injected through the bronchial arteries to penetrate to all parts of the lung than when the mass is injected through the pulmonary artery; but when accomplished, the injection reaches to all capillaries including those of the pleura, the only vessels remaining uninjected being the larger trunks of the pulmonary artery. On the other hand, the injection of the bronchial vessels by way of the pulmonary arteries is not complete with normal pressure, but occurs rapidly when a high pulmonary pressure is employed. It is therefore probable that either circulation can suffice for the simple nutritive demands of the lung if the other system is interfered with. It has been shown that embolism of the pulmonary artery, without other circulatory disturbance, does not lead to necrosis of the affected area of the lung, but it is probable that the preservation of circulation is not due to collateral bronchial circulation so much as to the free anastomosis and early division into capillaries of the pulmonary artery. In support of this statement is the fact that the appearance is not altered when the bronchials are ligated at their origin. The same ligation shows no subsequent interference with the nutrition of the bronchi up to a period of five weeks, demonstrating that the pulmonary circulation is sufficient to provide for the nutrition of the bronchi. If, however, as Virchow has shown, the pulmonary artery supplying an entire lobe be occluded, the bronchial circulation can and does suffice for the nutrition of the lobe. In the case of the occlusion of a branch of the pulmonary artery the pressure in the area interfered with does not sink to zero because of the collateral circulation in this area; whereas, if the main trunk is occluded no collateral supply is available, the pressure sinks to zero, and the bronchial artery becomes available as a source of blood supply. It must be remembered that the lung tissue, as a whole, has ready access to oxygen and this gas is the nutritive element acquired by the blood in the lungs. From these studies it would appear that the part of the lung tissue not in intimate contact with oxygen in the air is supplied by oxygenated blood of the bronchial arteries, and that the tissues through which the pulmonary blood circulates take up whatever organized nutriment they need from the pulmonary blood and possibly provide for their oxygen and carbon dioxide interchange (which must be very slight) either directly with the alveolar air, or by finding sufficient oxygen in the venous blood of the pulmonary artery. The studies of the injected specimens confirm Küttner's findings of a very rapid breaking up of the pulmonary artery into capillaries. In all the specimens studied it was found that although the pleural vessels can be injected by way of the bronchial arteries when there is zero pressure in the pulmonary arteries, yet when the two sets of vessels are injected simultaneously in the dog, the pleural vessels invariably derive their supply of injection mass from the pulmonary artery.

scholarly journals Oxygen-Sensitivity and Pulmonary Selectivity of Vasodilators as Potential Drugs for Pulmonary Hypertension

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 155
Author(s):  
Daniel Morales-Cano ◽  
Bianca Barreira ◽  
Beatriz De Olaiz Navarro ◽  
María Callejo ◽  
Gema Mondejar-Parreño ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Gas Exchange ◽  
Pulmonary Circulation ◽  
Pulmonary Arteries ◽  
Blood Perfusion ◽  
Mesenteric Arteries ◽  
Oxygen Sensitivity ◽  
Low Oxygen ◽  
Oxygen Selectivity

Current approved therapies for pulmonary hypertension (PH) aim to restore the balance between endothelial mediators in the pulmonary circulation. These drugs may exert vasodilator effects on poorly oxygenated vessels. This may lead to the derivation of blood perfusion towards low ventilated alveoli, i.e., producing ventilation-perfusion mismatch, with detrimental effects on gas exchange. The aim of this study is to analyze the oxygen-sensitivity in vitro of 25 drugs currently used or potentially useful for PH. Additionally, the study analyses the effectiveness of these vasodilators in the pulmonary vs. the systemic vessels. Vasodilator responses were recorded in pulmonary arteries (PA) and mesenteric arteries (MA) from rats and in human PA in a wire myograph under different oxygen concentrations. None of the studied drugs showed oxygen selectivity, being equally or more effective as vasodilators under conditions of low oxygen as compared to high oxygen levels. The drugs studied showed low pulmonary selectivity, being equally or more effective as vasodilators in systemic than in PA. A similar behavior was observed for the members within each drug family. In conclusion, none of the drugs showed optimal vasodilator profile, which may limit their therapeutic efficacy in PH.

scholarly journals The Role of JAK/STAT Molecular Pathway in Vascular Remodeling Associated with Pulmonary Hypertension

2021 ◽  
Vol 22 (9) ◽  
pp. 4980
Author(s):  
Inés Roger ◽  
Javier Milara ◽  
Paula Montero ◽  
Julio Cortijo
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Vascular Remodeling ◽  
Pulmonary Arteries ◽  
Clinical Manifestations ◽  
Different Types ◽  
Artery Remodeling ◽  
Stat Pathway ◽  
Pulmonary Artery Remodeling

Pulmonary hypertension is defined as a group of diseases characterized by a progressive increase in pulmonary vascular resistance (PVR), which leads to right ventricular failure and premature death. There are multiple clinical manifestations that can be grouped into five different types. Pulmonary artery remodeling is a common feature in pulmonary hypertension (PH) characterized by endothelial dysfunction and smooth muscle pulmonary artery cell proliferation. The current treatments for PH are limited to vasodilatory agents that do not stop the progression of the disease. Therefore, there is a need for new agents that inhibit pulmonary artery remodeling targeting the main genetic, molecular, and cellular processes involved in PH. Chronic inflammation contributes to pulmonary artery remodeling and PH, among other vascular disorders, and many inflammatory mediators signal through the JAK/STAT pathway. Recent evidence indicates that the JAK/STAT pathway is overactivated in the pulmonary arteries of patients with PH of different types. In addition, different profibrotic cytokines such as IL-6, IL-13, and IL-11 and growth factors such as PDGF, VEGF, and TGFβ1 are activators of the JAK/STAT pathway and inducers of pulmonary remodeling, thus participating in the development of PH. The understanding of the participation and modulation of the JAK/STAT pathway in PH could be an attractive strategy for developing future treatments. There have been no studies to date focused on the JAK/STAT pathway and PH. In this review, we focus on the analysis of the expression and distribution of different JAK/STAT isoforms in the pulmonary arteries of patients with different types of PH. Furthermore, molecular canonical and noncanonical JAK/STAT pathway transactivation will be discussed in the context of vascular remodeling and PH. The consequences of JAK/STAT activation for endothelial cells and pulmonary artery smooth muscle cells’ proliferation, migration, senescence, and transformation into mesenchymal/myofibroblast cells will be described and discussed, together with different promising drugs targeting the JAK/STAT pathway in vitro and in vivo.

scholarly journals Structural alterations and markers of endothelial activation in pulmonary and bronchial arteries in fatal asthma

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Renata Calciolari Rossi ◽  
Raquel Anonni ◽  
Diogenes Seraphim Ferreira ◽  
Luiz Fernando Ferraz da Silva ◽  
Thais Mauad
Keyword(s):  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Pulmonary Arteries ◽  
Endothelial Activation ◽  
Bronchial Arteries ◽  
Activation Markers ◽  
Asthma Attack ◽  
Collagen Iii ◽  
Asthma Patients ◽  
Fatal Asthma

Abstract Background There is interest in better understanding vessel pathology in asthma, given the findings of loss of peripheral vasculature associated with disease severity by imaging and altered markers of endothelial activation. To date, vascular changes in asthma have been described mainly at the submucosal capillary level of the bronchial microcirculation, with sparse information available on the pathology of bronchial and pulmonary arteries. The aim of this study was to describe structural and endothelial activation markers in bronchial arteries (BAs) and pulmonary arteries (PAs) of asthma patients who died during a fatal asthma attack. Methods Autopsy lung tissue was obtained from 21 smoking and non-smoking patients who died of an asthma attack and nine non-smoking control patients. Verhoeff–Masson trichrome staining was used to analyse the structure of arteries. Using immuno-histochemistry and image analyses, we quantified extracellular matrix (ECM) components (collagen I, collagen III, versican, tenascin, fibronectin, elastic fibres), adhesion molecules [vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)] and markers of vascular tone/dysfunction [endothelin-1 (ET-1) and angiotensin II type 2 receptor (AT2)] in PAs and BAs. Results There were no significant differences in ECM components, ICAM-1, ET-1 or AT2 between asthma patients and controls. Smoking asthma patients presented with decreased content of collagen III in both BA (p = 0.046) and PA (p = 0.010) walls compared to non-smoking asthma patients. Asthma patients had increased VCAM-1 content in the BA wall (p = 0.026) but not in the PA wall. Conclusion Our data suggest that the mechanisms linking asthma and arterial functional abnormalities might involve systemic rather than local mediators. Loss of collagen III in the PA was observed in smoking asthma patients, and this was compatible with the degradative environment induced by cigarette smoking. Our data also reinforce the idea that the mechanisms of leukocyte efflux via adhesion molecules differ between bronchial and pulmonary circulation, which might be relevant to understanding and treating the distal lung in asthma.

Perspectives on endothelial-to-mesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertension

2007 ◽  
Vol 293 (1) ◽  
pp. L1-L8 ◽  
Author(s):  
Enrique Arciniegas ◽  
Maria G. Frid ◽  
Ivor S. Douglas ◽  
Kurt R. Stenmark
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Vascular Remodeling ◽  
Serine Proteases ◽  
Structural Changes ◽  
Transforming Growth Factor ◽  
Pulmonary Arteries ◽  
Potential Contribution ◽  
Mesenchymal Transition ◽  
Endothelial Mesenchymal Transition

All forms of pulmonary hypertension are characterized by structural changes in pulmonary arteries. Increased numbers of cells expressing α-smooth muscle (α-SM) actin is a nearly universal finding in the remodeled artery. Traditionally, it was assumed that resident smooth muscle cells were the exclusive source of these newly appearing α-SM actin-expressing cells. However, rapidly emerging experimental evidence suggests other, alternative cellular sources of these cells. One possibility is that endothelial cells can transition into mesenchymal cells expressing α-SM actin and that this process contributes to the accumulation of SM-like cells in vascular pathologies. We review the evidence that endothelial-mesenchymal transition is an important contributor to cardiac and vascular development as well as to pathophysiological vascular remodeling. Recent work has provided evidence for the role of transforming growth factor-β, Wnt, and Notch signaling in this process. The potential roles of matrix metalloproteinases and serine proteases are also discussed. Importantly, endothelial-mesenchymal transition may be reversible. Thus insights into the mechanisms controlling endothelial-mesenchymal transition are relevant to vascular remodeling and are important as we consider new therapies aimed at reversing pulmonary vascular remodeling.

scholarly journals The movement ecology of seagrasses

2014 ◽  
Vol 281 (1795) ◽  
pp. 20140878 ◽  
Author(s):  
Kathryn McMahon ◽  
Kor-jent van Dijk ◽  
Leonardo Ruiz-Montoya ◽  
Gary A. Kendrick ◽  
Siegfried L. Krauss ◽  
...  
Keyword(s):  
Life History ◽  
Clonal Growth ◽  
Movement Ecology ◽  
Future Research ◽  
The Novel ◽  
Long Distance ◽  
Spatial And Temporal Scales ◽  
Life History Stages ◽  
Research Areas ◽  
Time Movement

A movement ecology framework is applied to enhance our understanding of the causes, mechanisms and consequences of movement in seagrasses: marine, clonal, flowering plants. Four life-history stages of seagrasses can move: pollen, sexual propagules, vegetative fragments and the spread of individuals through clonal growth. Movement occurs on the water surface, in the water column, on or in the sediment, via animal vectors and through spreading clones. A capacity for long-distance dispersal and demographic connectivity over multiple timeframes is the novel feature of the movement ecology of seagrasses with significant evolutionary and ecological consequences. The space–time movement footprint of different life-history stages varies. For example, the distance moved by reproductive propagules and vegetative expansion via clonal growth is similar, but the timescales range exponentially, from hours to months or centuries to millennia, respectively. Consequently, environmental factors and key traits that interact to influence movement also operate on vastly different spatial and temporal scales. Six key future research areas have been identified.

Introduction and Preliminary Investigation of Buoyancy Assisted Robots That Are Cheap, Safe, and Will Never Fall Down

2021 ◽  
Author(s):  
Matthew David Williams ◽  
Dennis Hong
Keyword(s):  
Genetic Algorithm ◽  
Preliminary Analysis ◽  
Preliminary Investigation ◽  
Research Work ◽  
Legged Robots ◽  
Dynamical Analysis ◽  
Future Research ◽  
The Novel ◽  
Drag Forces ◽  
New Family

Abstract We introduce and define a new family of mobile robots called BAR (Buoyancy Assisted Robots) that are cheap, safe, and will never fall down. BARs utilize buoyancy from lighter-than-air gases as a way to support the weight of the robot for locomotion. A new BAR robot named BLAIR (Buoyant Legged Actuated Inverted Robot) whose buoyancy is greater than its weight is also presented in this paper. BLAIRs can walk “upside-down” on the ceiling, providing unique advantages that no other robot platforms can. Unlike other legged robots, the mechanics of how BARs walk is fundamentally different. We also perform a preliminary investigation for BARs. This includes comparing safety, cost, and energy consumption with other commercially available robots. Additionally, the preliminary investigation also includes analyzing previous works relating to BARs. A dynamical analysis is performed on the novel robot BLAIR. This is presented to show the impacts of buoyant and drag forces on BLAIRs. Preliminary analysis with the prevalence of drag is presented with simulations using a genetic algorithm and simulations. Results show that BARs with different mechanisms prefer different styles of walking gaits such as prancing or skipping. This work lays the foundation for future research work on the gaits for BARs.

Effects of lipotoxicity on a novel insulin-secreting human pancreatic β-cell line, 1.1B4

2013 ◽  
Vol 394 (7) ◽  
pp. 909-918 ◽  
Author(s):  
Srividya Vasu ◽  
Neville H. McClenaghan ◽  
Jane T. McCluskey ◽  
Peter R. Flatt
Keyword(s):  
Mrna Expression ◽  
Cell Line ◽  
Molecular Mechanisms ◽  
Endoplasmic Reticulum Stress Response ◽  
Future Research ◽  
The Novel ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Expression Of Genes ◽  
Cellular Ca

Abstract The novel insulin-secreting human pancreatic β-cell line, 1.1B4, demonstrates stability in culture and many of the secretory functional attributes of human pancreatic β-cells. This study investigated the cellular responses of 1.1B4 cells to lipotoxicity. Chronic 18-h exposure of 1.1B4 cells to 0.5 mm palmitate resulted in decreased cell viability and insulin content. Secretory responses to classical insulinotropic agents and cellular Ca2+ handling were also impaired. Palmitate decreased glucokinase activity and mRNA expression of genes involved in secretory function but up-regulated mRNA expression of HSPA5, EIF2A, and EIF2AK3, implicating activation of the endoplasmic reticulum stress response. Palmitate also induced DNA damage and apoptosis of 1.1B4 cells. These responses were accompanied by increased gene expression of the antioxidant enzymes SOD1, SOD2, CAT and GPX1. This study details molecular mechanisms underlying lipotoxicity in 1.1B4 cells and indicates the potential value of the novel β-cell line for future research.

scholarly journals Targeted Next Generation Sequencing Reveals a Third Breakpoint Cluster Region and New Partner Genes in the KMT2A Recombinome

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3327-3327
Author(s):  
Claus Meyer ◽  
Patrizia Larghero ◽  
Bruno Lopes ◽  
Aurélie Caye-Eude ◽  
Hélène Cavé ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Multiplex Pcr ◽  
Conflicts Of Interest ◽  
Future Research ◽  
Striking Difference ◽  
Elongation Complex ◽  
Long Distance ◽  
Acute Leukemias ◽  
Breakpoint Cluster Region ◽  
Cluster Region

Abstract Chromosomal rearrangements of the KMT2A gene are associated with acute leukemias and myelodysplastic syndromes. The large number of known KMT2A fusions (>100) renders a precise diagnosis a demanding task. More than 50% of all KMT2A partner genes have been analyzed at the DCAL, including the novel partner genes BCAS4, FAM13A, RANBP3, and STK4. Even though all KMT2A rearrangements are associated with high-risk acute leukemia, the outcome (poor or very poor) is influenced by the partner gene. So far, we have analyzed more than 3,200 patients positive for a KMT2A rearrangement. The breakpoints of these cases are located mainly in the major breakpoint cluster region (bcr1) and to a small extent in the recently described minor bcr (bcr2). A small number of breakpoints were also found outside of these two bcrs. Most of these patients were analyzed by long distance inverse (LDI)- or multiplex-PCR which only cover bcr1. More recently, we used targeted KMT2A-NGS with whole gene coverage in over 450 patients, which was initially applied selectively in patients negative by LDI- and multiplex-PCR and then used more widely. Within the KMT2A-NGS group, 410 patients had bcr1 breakpoints mainly between the KMT2A exons 7 and 13, while 46 patients bcr2 breakpoints mainly between exons 20 and 24. Of note, five patients had their breakpoint outside of these two bcrs: three of them within intron 2 and no functional KMT2A rearrangement; the other two within intron 35 and intron 36, fusing almost the whole KMT2A gene in frame to the respective partner genes ARHGEF12 and MLLT4. These two breakpoints may define a third and rare bcr (bcr3), although further cases are needed to support this hypothesis. Interestingly, 70 patients displayed a 3'-KMT2A deletion, indicating that the number of terminal deletions is higher than described previously. Two patients had a 5'-KMT2A deletion. All deletions started or ended in bcr1 and bcr2. We also observed a striking difference in the distribution of partner genes between bcr1 and bcr2. The most frequent translocation partners fused to bcr1 sites are transcription factors, while the partner genes linked to bcr2 sites generally code for cytosolic proteins. In bcr1, the 4 most frequent partner genes AFF1, MLLT3, MLLT1, and MLLT10, found in 80% of cases, all code for transcription factors that are part of the super elongation complex (SEC). These fusions therefore all lead to disruption of the hematopoietic lineage commitment. In contrast in bcr2, 3 partner genes USP2, MLLT4, and USP8 account for 85% of the cases. USP2 and USP8 are ubiquitin specific peptidases involved in cell signaling and exclusively fused to bcr2 in KMT2A. While MLLT4 is found as a partner in bcr1, bcr2 and bcr3 fusions; unlike other recurrent KMT2A partners linked to bcr1, it is not a transcription factor and it exerts oncogenic potential via dimerization like other cytosolic partners. We hypothesize that the oncogenic properties of USP2 and USP8 are dependent on dimerization like MLLT4 and that the most frequent fusions involving at different bcrs favor different oncogenic mechanisms: bcr1 transactivation and bcr2 dimerization. Further studies are needed to explain why USP2 and USP8 are exclusively associated with bcr2, and why the most frequent partner genes AFF1 and MLLT3 of the bcr1 are less frequent in bcr2. In conclusion, targeted NGS combined with bioinformatic analysis has expanded our knowledge of the KMT2A recombinome to include more fusion partners and has generated new hypotheses for future research on oncogenic mechanisms. Disclosures No relevant conflicts of interest to declare.

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