scholarly journals Unique Aspects of the Developing Lung Circulation: Structural Development and Regulation of Vasomotor Tone

2016 ◽  
Vol 6 (4) ◽  
pp. 407-425 ◽  
Author(s):  
Yuangsheng Gao ◽  
David N. Cornfield ◽  
Kurt R. Stenmark ◽  
Bernard Thébaud ◽  
Steven H. Abman ◽  
...  
Keyword(s):  
Lung Development ◽  
Lung Diseases ◽  
Vascular Tone ◽  
Current Knowledge ◽  
Normal Lung ◽  
Pulmonary Vasculature ◽  
Structural Development ◽  
Vasomotor Tone ◽  
Disease States ◽  
Vasculogenesis And Angiogenesis

This review summarizes our current knowledge on lung vasculogenesis and angiogenesis during normal lung development and the regulation of fetal and postnatal pulmonary vascular tone. In comparison to that of the adult, the pulmonary circulation of the fetus and newborn displays many unique characteristics. Moreover, altered development of pulmonary vasculature plays a more prominent role in compromised pulmonary vasoreactivity than in the adult. Clinically, a better understanding of the developmental changes in pulmonary vasculature and vasomotor tone and the mechanisms that are disrupted in disease states can lead to the development of new therapies for lung diseases characterized by impaired alveolar structure and pulmonary hypertension.

scholarly journals In vitro models of fetal lung development to enhance research into congenital lung diseases

2021 ◽  
Author(s):  
Soichi Shibuya ◽  
Jessica Allen-Hyttinen ◽  
Paolo De Coppi ◽  
Federica Michielin
Keyword(s):  
Lung Development ◽  
Lung Diseases ◽  
Ex Vivo ◽  
Fetal Lung ◽  
Branching Morphogenesis ◽  
In Vitro Models ◽  
Normal Lung ◽  
Novel Therapeutic Strategies ◽  
Pseudoglandular Stage

Abstract Purpose This paper aims to build upon previous work to definitively establish in vitro models of murine pseudoglandular stage lung development. These can be easily translated to human fetal lung samples to allow the investigation of lung development in physiologic and pathologic conditions. Methods Lungs were harvested from mouse embryos at E12.5 and cultured in three different settings, i.e., whole lung culture, mesenchyme-free epithelium culture, and organoid culture. For the whole lung culture, extracted lungs were embedded in Matrigel and incubated on permeable filters. Separately, distal epithelial tips were isolated by firstly removing mesothelial and mesenchymal cells, and then severing the tips from the airway tubes. These were then cultured either in branch-promoting or self-renewing conditions. Results Cultured whole lungs underwent branching morphogenesis similarly to native lungs. Real-time qPCR analysis demonstrated expression of key genes essential for lung bud formation. The culture condition for epithelial tips was optimized by testing different concentrations of FGF10 and CHIR99021 and evaluating branching formation. The epithelial rudiments in self-renewing conditions formed spherical 3D structures with homogeneous Sox9 expression. Conclusion We report efficient protocols for ex vivo culture systems of pseudoglandular stage mouse embryonic lungs. These models can be applied to human samples and could be useful to paediatric surgeons to investigate normal lung development, understand the pathogenesis of congenital lung diseases, and explore novel therapeutic strategies.

Effects of hypoxia and vascular tone on endothelium-dependent and -independent responses in developing lungs

1995 ◽  
Vol 79 (3) ◽  
pp. 824-830 ◽  
Author(s):  
J. B. Gordon ◽  
F. R. Martinez ◽  
D. C. O'Donnell ◽  
M. L. Tod
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Pulmonary Vascular Resistance ◽  
Oxygen Tension ◽  
Vascular Tone ◽  
Developmental Differences ◽  
Pulmonary Vasculature ◽  
Vasomotor Tone ◽  
Pulmonary Arterial ◽  
Dose Responses

Both increases and decreases in endothelium-derived nitric oxide (EDNO) activity have been described in the developing pulmonary vasculature. We hypothesized that differences in baseline vasomotor tone and/or oxygen tension may contribute to this variability. Pulmonary arterial dose responses to endothelium-dependent and -independent vasodilators acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were measured in indomethacin-treated lungs of 1- to 2-day-old (2D) and 1-mo-old (1M) lambs. During 4% O2 ventilation, baseline pulmonary vascular resistance (PVR) and the dilator response to both ACh and SNP were greater in 2D lungs. However, when baseline PVR values were matched at both ages during either hypoxia or infusion of a thromboxane mimetic under normoxic conditions, developmental differences in ACh-induced vasodilation were minimal. Furthermore, hypoxia itself did not alter the responses to ACh in 2D lungs. In contrast, SNP caused greater vasodilation in 2D than in 1M lungs regardless of baseline PVR. These data and studies suggest that whereas high PVR enhances EDNO synthesis, responsiveness to ENDO decreases as synthesis of ENDO increases in developing lungs studied under basal conditions.

scholarly journals S1P2 receptor-dependent Rho-kinase activation mediates vasoconstriction in the murine pulmonary circulation induced by sphingosine 1-phosphate

2010 ◽  
Vol 299 (1) ◽  
pp. L137-L145 ◽  
Author(s):  
William S. Szczepaniak ◽  
Bruce R. Pitt ◽  
Bryan J. McVerry
Keyword(s):  
Vascular Tone ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Receptor Expression ◽  
Normal Lung ◽  
Pulmonary Vasculature ◽  
Mouse Lung ◽  
Receptor Antagonism ◽  
Sphingosine 1 Phosphate

Vasoactive properties of sphingosine 1-phosphate (S1P) have been demonstrated by many investigators to vary in systemic vascular beds. These variations appear to reflect differential S1P receptor expression in the vasculature of these tissues. Although S1P has been demonstrated to enhance endothelial barrier function, induce airway hyperresponsiveness, and modulate immune responses in the lung, the pulmonary vasomotor effects of S1P remain poorly defined. In the present study, we sought to define the vasoregulatory effects of S1P in the pulmonary vasculature and to elucidate the underlying mechanisms operative in effecting the response in the intact lung. S1P (10 μM) increased pulmonary vascular resistance (PVR) by 36% in the isolated perfused mouse lung. S1P-induced vasoconstriction was reduced by 64% by concomitant administration of the Rho-kinase inhibitor Y27632 (10 μM). Similarly, the S1P response was attenuated by >50% after S1P2 receptor antagonism (JTE-013; 10 μM) and in S1P2 receptor null mice. In contrast, S1P3 receptor antagonism (VPC23019; 10 μM) had no effect on the contractile response to S1P. Furthermore, we confirmed the role of Rho-kinase as an important regulator of basal vasomotor tone in the isolated perfused mouse lung. These results suggest that S1P is capable of altering pulmonary vascular tone in vivo and may play an important role in the modulation of pulmonary vascular tone both in the normal lung and under pathological conditions.

The impact of sex and sex hormones on lung physiology and disease: lessons from animal studies

2007 ◽  
Vol 293 (2) ◽  
pp. L272-L278 ◽  
Author(s):  
Michelle A. Carey ◽  
Jeffrey W. Card ◽  
James W. Voltz ◽  
Dori R. Germolec ◽  
Kenneth S. Korach ◽  
...  
Keyword(s):  
Sex Hormones ◽  
Lung Development ◽  
Lung Diseases ◽  
Animal Studies ◽  
Airway Disease ◽  
Allergic Airway Disease ◽  
Normal Lung ◽  
Lung Physiology ◽  
Injury Models ◽  
The Impact

Numerous animal studies have revealed significant effects of sex and sex hormones on normal lung development, lung physiology, and various lung diseases. The primary goal of this review is to summarize knowledge to date on the effects of sex and sex hormones on lung development, physiology, and disease in animals. Specific emphasis will be placed on fibrosis, allergic airway disease, acute lung injury models, respiratory infection, and lung toxicology studies.

scholarly journals Distal angiogenesis: a new concept for lung vascular morphogenesis

2005 ◽  
Vol 288 (1) ◽  
pp. L141-L149 ◽  
Author(s):  
Marta Canis Parera ◽  
Marieke van Dooren ◽  
Marjon van Kempen ◽  
Ronald de Krijger ◽  
Frank Grosveld ◽  
...  
Keyword(s):  
Lung Development ◽  
Vascular Network ◽  
Pulmonary Vasculature ◽  
Capillary Networks ◽  
Vascular Morphogenesis ◽  
Early Embryonic Stage ◽  
Morphological Sign ◽  
Vasculogenesis And Angiogenesis ◽  
Terminal Buds ◽  
Section Analysis

Although several molecular players have been described that play a role during the early phases of lung development, it is still unknown how the vasculature develops in relation to the airways. Two opposing models describe development of lung vasculature: one suggests that both vasculogenesis and angiogenesis are involved, whereas the second describes vasculogenesis as the primary mechanism. Therefore, we examined the development of the murine pulmonary vasculature through a morphological analysis from the onset of lung development [9.5 days postcoital (dpc)] until the pseudoglandular stage (13.5 dpc). We analyzed fetal lungs of Tie2-LacZ transgenic mice as well as serial sections of wild-type lungs stained with endothelial-specific antibodies (Flk-1, Fli-1, and PECAM-1). Embryos were processed with intact blood circulation to maintain the integrity of the vasculature; hence individual vessels could be identified with accuracy through serial section analysis. Furthermore, circulating primitive erythrocytes, formed exclusively by the blood islands in the yolk sac, are trapped in vessels during fixation, which proves the connection with the embryonic circulation. We report that from the first morphological sign of lung development, a clear vascular network exists that is in contact with the embryonic circulation. We propose distal angiogenesis as a new concept for early pulmonary vascular morphogenesis. In this model, capillary networks surround the terminal buds and expand by formation of new capillaries from preexisting vessels as the lung bud grows. The fact that at an early embryonic stage a complete vascular network exists may be important for the general understanding of embryonic development.

scholarly journals Poor Cognitive Function Is Associated with Obstructive Lung Diseases in Taiwanese Adults

2021 ◽  
Vol 18 (5) ◽  
pp. 2344
Author(s):  
Sun-Wung Hsieh ◽  
Da-Wei Wu ◽  
Chih-Wen Wang ◽  
Szu-Chia Chen ◽  
Chih-Hsing Hung ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Lung Function ◽  
Lung Diseases ◽  
Mmse Score ◽  
Multivariable Analysis ◽  
Forced Expiratory Volume ◽  
Normal Lung ◽  
Obstructive Lung Diseases ◽  
Normal Lung Function ◽  
Function Group

Previous studies have reported an association between the impairment of cognitive performance and lung diseases. However, whether obstructive or restrictive lung diseases have an impact on cognitive function is still inconclusive. We aimed to investigate the association between cognitive function and obstructive or restrictive lung diseases in Taiwanese adults using the Mini-Mental State Examination (MMSE). In this study, we used data from the Taiwan Biobank. Cognitive function was evaluated using the MMSE. Spirometry measurements of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained to assess lung function. Participants were classified into three groups according to lung function, namely, normal, restrictive, and obstructive lung function. In total, 683 patients enrolled, of whom 357 participants had normal lung function (52.3%), 95 had restrictive lung function (13.9%), and 231 had obstructive lung function (33.8%). Compared to the normal lung function group, the obstructive lung function group was associated with a higher percentage of cognitive impairment (MMSE < 24). In multivariable analysis, a low MMSE score was significantly associated with low FVC, low FEV1, and low FEV1/FVC. Furthermore, a low MMSE score was significantly associated with low FEV1 in the participants with FEV1/FVC < 70%, whereas MMSE was not significantly associated with FVC in the participants with FEV1/FVC ≥ 70%. Our results showed that a low MMSE score was associated with low FEV1, low FVC and low FEV1/FVC. Furthermore, a low MMSE score was associated with obstructive lung diseases but not with restrictive lung diseases.

Neurotrophic factors and their receptors in lung development and implications in lung diseases

2021 ◽  
Author(s):  
Limor Rubin ◽  
Collin T. Stabler ◽  
Adi Schumacher-Klinger ◽  
Cezary Marcinkiewicz ◽  
Peter I. Lelkes ◽  
...  
Keyword(s):  
Neurotrophic Factors ◽  
Lung Development ◽  
Lung Diseases

scholarly journals A Crosstalk between Diet, Microbiome and microRNA in Epigenetic Regulation of Colorectal Cancer

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2428
Author(s):  
Małgorzata Guz ◽  
Witold Jeleniewicz ◽  
Anna Malm ◽  
Izabela Korona-Glowniak
Keyword(s):  
Colorectal Cancer ◽  
Gastrointestinal Tract ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Current Knowledge ◽  
Vital Role ◽  
Disease States ◽  
Health And Disease ◽  
Dietary Components ◽  
Non Coding Rnas

A still growing interest between human nutrition in relation to health and disease states can be observed. Dietary components shape the composition of microbiota colonizing our gastrointestinal tract which play a vital role in maintaining human health. There is a strong evidence that diet, gut microbiota and their metabolites significantly influence our epigenome, particularly through the modulation of microRNAs. These group of small non-coding RNAs maintain cellular homeostasis, however any changes leading to impaired expression of miRNAs contribute to the development of different pathologies, including neoplastic diseases. Imbalance of intestinal microbiota due to diet is primary associated with the development of colorectal cancer as well as other types of cancers. In the present work we summarize current knowledge with particular emphasis on diet-microbiota-miRNAs axis and its relation to the development of colorectal cancer.

scholarly journals The Mechanosensitive Ion Channel TRPV4 is a Regulator of Lung Development and Pulmonary Vasculature Stabilization

2018 ◽  
Vol 11 (5) ◽  
pp. 309-320 ◽  
Author(s):  
Joshua T. Morgan ◽  
Wade G. Stewart ◽  
Robert A. McKee ◽  
Jason P. Gleghorn
Keyword(s):  
Ion Channel ◽  
Lung Development ◽  
Pulmonary Vasculature ◽  
Mechanosensitive Ion Channel

scholarly journals Mechanisms and consequences of oxidative stress in lung disease: therapeutic implications for an aging populace

2018 ◽  
Vol 314 (4) ◽  
pp. L642-L653 ◽  
Author(s):  
Louise Hecker
Keyword(s):  
Oxidative Stress ◽  
Lung Disease ◽  
Lung Diseases ◽  
The Elderly ◽  
Therapeutic Strategies ◽  
Rapid Expansion ◽  
Pulmonary Diseases ◽  
Normal Lung ◽  
Incidence And Mortality ◽  
And Oxidative Stress

The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility. Here, we focus on three lung diseases for which aging is a significant risk factor: acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Preclinical and clinical development for redox- and senescence-altering therapeutic strategies are discussed, as well as scientific advancements that may direct current and future therapeutic development. A deeper understanding of how aging impacts normal lung function, redox balance, and injury-repair processes will inspire the development of new therapies to prevent and/or reverse age-associated pulmonary diseases, and ultimately increase health span and longevity. This review is intended to encourage basic, clinical, and translational research that will bridge knowledge gaps at the intersection of aging, oxidative stress, and lung disease to fuel the development of more effective therapeutic strategies for lung diseases that disproportionately afflict the elderly.

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