scholarly journals Pulmonary hypertension secondary to pulmonary fibrosis: clinical data, histopathology and molecular insights

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Grégoire Ruffenach ◽  
Jason Hong ◽  
Mylène Vaillancourt ◽  
Lejla Medzikovic ◽  
Mansoureh Eghbali
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Fibrosis ◽  
Vascular Remodeling ◽  
Strong Predictor ◽  
Lung Parenchyma ◽  
Vascular Bed ◽  
Hypoxic Vasoconstriction ◽  
Co Morbidity ◽  
High Prevalence ◽  
Molecular Pathophysiology

AbstractPulmonary hypertension (PH) developing secondarily in pulmonary fibrosis (PF) patients (PF-PH) is a frequent co-morbidity. The high prevalence of PH in PF patients is very concerning since the presence of PH is a strong predictor of mortality in PF patients. Until recently, PH was thought to arise solely from fibrotic destruction of the lung parenchyma, leading to hypoxic vasoconstriction and loss of vascular bed density. Thus, potential cellular and molecular dysregulation of vascular remodeling as a driver of PF-PH has been under-investigated. The recent demonstrations that there is no correlation between the severity of the fibrosis and development of PH, along with the finding that significant vascular histological and molecular differences exist between patients with and without PH have shifted the etiological paradigm of PF-PH. This review aims to provide a comprehensive translational overview of PH in PF patients from clinical diagnosis and outcome to the latest understanding of the histology and molecular pathophysiology of PF-PH.

scholarly journals The prevalence of pulmonary hypertension assessed using the pulmonary vein‐to‐right pulmonary artery ratio and its association with survival in West Highland white terriers with canine idiopathic pulmonary fibrosis

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Elodie Roels ◽  
Aline Fastrès ◽  
Anne-Christine Merveille ◽  
Géraldine Bolen ◽  
Erik Teske ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Pulmonary Artery ◽  
Pulmonary Vein ◽  
Survival Data ◽  
Study Objective ◽  
Time Motion ◽  
Co Morbidity ◽  
Right Pulmonary Artery

Abstract Background Pulmonary hypertension (PH) is a known co-morbidity in West Highland white terriers (WHWTs) affected with canine idiopathic pulmonary fibrosis (CIPF). The pulmonary vein-to-right pulmonary artery ratio (PV/PA) has recently been described for the detection of pre-capillary PH in dogs. The objective of the present study was to estimate the prevalence of PH at diagnostic, in WHWTs affected with CIPF, by using PV/PA, in comparison with a group of healthy breed-matched controls (CTRLs). Additional study objective was to explore whether the presence of PH at initial diagnosis of CIPF impacted survival time in dogs treated with sildenafil. Results Twenty-five client-owned WHWTs presented with CIPF and 19 CTRLs were included in the study. PV/PA in either two-dimensional mode (2D) or time-motion mode or both were measured from cineloops in each dog. Dogs were classified according to PV/PA value into non/mild PH (PV/PA measured in 2D ≥ 0.7) or moderate/severe PH (PV/PA < 0.7). Survival data of WHWTs affected with CIPF were extracted from medical record to assess association between presence of PH at diagnosis and outcome. 60 % overall prevalence for moderate/severe PH was estimated in this cohort of WHWTs presented with CIPF vs. 5 % in CTRLS (P = 0.0002). The presence of moderate/severe PH at initial presentation was not associated with survival. Conclusions Results of the present study confirm a high prevalence of PH at diagnosis in WHWTs affected with CIPF and highlight the utility of PV/PA as a non-invasive surrogate for assessment of PH in this population.

scholarly journals Orotracheal treprostinil administration attenuates bleomycin-induced lung injury, vascular remodeling, and fibrosis in mice

2019 ◽  
Vol 9 (4) ◽  
pp. 204589401988195
Author(s):  
Ioanna Nikitopoulou ◽  
Nikolaos Manitsopoulos ◽  
Anastasia Kotanidou ◽  
Xia Tian ◽  
Aleksandar Petrovic ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Vascular Remodeling ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Lung Mechanics ◽  
Lung Pathology ◽  
Prostacyclin Analogue

Pulmonary fibrosis is a progressive disease characterized by disruption of lung architecture and deregulation of the pulmonary function. Prostacyclin, a metabolite of arachidonic acid, is a potential disease mediator since it exerts anti-inflammatory and anti-fibrotic actions. We investigated the effect of treprostinil, a prostacyclin analogue, in bleomycin-induced experimental pulmonary fibrosis. Bleomycin sulfate or saline was administrated intratracheally to mice ( n = 9–10/group) at day 0. Orotracheal aspiration of treprostinil or vehicle was administered daily and started 24 h prior to bleomycin challenge. Evaluation of lung pathology was performed in tissue samples and bronchoalveolar lavage fluid collected 7, 14 and 21 days after bleomycin exposure. Lung injury was achieved due to bleomycin exposure at all time points as indicated by impaired lung mechanics, pathologic lung architecture (from day 14), and cellular and protein accumulation in the alveolar space accompanied by a minor decrease in lung tissue VE-cadherin at day 14. Treprostinil preserved lung mechanics, and reduced lung inflammation, fibrosis, and vascular remodeling (day 21); reduced cellularity and protein content of bronchoalveolar lavage fluid were additionally observed with no significant effect on VE-cadherin expression. Bleomycin-induced collagen deposition was attenuated by treprostinil from day 14, while treprostinil involvement in regulating inflammatory processes appears mediated by NF-κB signaling. Overall, prophylactic administration of treprostinil, a stable prostacyclin analogue, maintained lung function, and prevented bleomycin-induced lung injury, and fibrosis, as well as vascular remodeling, a hallmark of pulmonary hypertension. This suggests potential therapeutic efficacy of treprostinil in pulmonary fibrosis and possibly in pulmonary hypertension related to chronic lung diseases.

scholarly journals Herpes Virus Infection Is Associated with Vascular Remodeling and Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e55715 ◽  
Author(s):  
Fiorella Calabrese ◽  
Anja Kipar ◽  
Francesca Lunardi ◽  
Elisabetta Balestro ◽  
Egle Perissinotto ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Virus Infection ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Vascular Remodeling ◽  
Herpes Virus ◽  
Herpes Virus Infection ◽  
Herpès Virus

scholarly journals Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis

2013 ◽  
Vol 12 (3) ◽  
pp. 127-134 ◽  
Author(s):  
Belinda N. Rivera-Lebron
Keyword(s):  
Pulmonary Hypertension ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Fold Increase ◽  
Right Heart Catheterization ◽  
Noninvasive Testing ◽  
Heart Catheterization ◽  
Risk Of Death ◽  
Hypoxic Vasoconstriction ◽  
Hemodynamic Assessment

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with a variable natural history. Pulmonary hypertension (PH) is frequently found in patients with IPF and is associated with an almost 3-fold increase in the risk of death. Pulmonary hypoxic vasoconstriction plays an important role in the pathogenesis of PH in IPF (PH-IPF), although it has become clear that it is not the only mechanism involved. While invasive right heart catheterization is the gold standard modality of hemodynamic assessment, there has been increasing interest in noninvasive testing, such as Doppler echocardiogram, as complementary methods of assessing right ventricular function in these patients. While the expanding array of pharmacologic options for the treatment of pulmonary arterial hypertension has engendered increased interest in the application of these therapies for PH-IPF, supportive evidence for benefit is lacking.

Quantitative Microscopic Comparison of the Organization of the Lung in Transgenic Mice Expressing Transforming Growth Factor-α (TGF-α)

1996 ◽  
Vol 54 ◽  
pp. 14-15
Author(s):  
C. G. Plopper ◽  
C. Helton ◽  
A. J. Weir ◽  
J. A. Whitsett ◽  
T. R. Korfhagen
Keyword(s):  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Transgenic Mice ◽  
Blood Vessels ◽  
Lung Parenchyma ◽  
Lung Maturation ◽  
Alveolar Air ◽  
Parenchymal Tissue ◽  
Air Space ◽  
Conducting Airways

A wide variety of growth factors are thought to be involved in the regulation of pre- and postnatal lung maturation, including factors which bind to the epidermal growth factor receptor. Marked pulmonary fibrosis and enlarged alveolar air spaces have been observed in lungs of transgenic mice expressing human TGF-α under control of the 3.7 KB human SP-C promoter. To test whether TGF-α alters lung morphogenesis and cellular differentiation, we examined morphometrically the lungs of adult (6-10 months) mice derived from line 28, which expresses the highest level of human TGF-α transcripts among transgenic lines. Total volume of lungs (LV) fixed by airway infusion at standard pressure was similar in transgenics and aged-matched non-transgenic mice (Fig. 1). Intrapulmonary bronchi and bronchioles made up a smaller percentage of LV in transgenics than in non-transgenics (Fig. 2). Pulmonary arteries and pulmonary veins were a smaller percentage of LV in transgenic mice than in non-transgenics (Fig. 3). Lung parenchyma (lung tissue free of large vessels and conducting airways) occupied a larger percentage of LV in transgenics than in non-transgenics (Fig. 4). The number of generations of branching in conducting airways was significantly reduced in transgenics as compared to non-transgenic mice. Alveolar air space size, as measured by mean linear intercept, was almost twice as large in transgenic mice as in non-transgenics, especially when different zones within the lung were compared (Fig. 5). Alveolar air space occupied a larger percentage of the lung parenchyma in transgenic mice than in non-transgenic mice (Fig. 6). Collagen abundance was estimated in histological sections as picro-Sirius red positive material by previously-published methods. In intrapulmonary conducting airways, collagen was 4.8% of the wall in transgenics and 4.5% of the wall in non-transgenic mice. Since airways represented a smaller percentage of the lung in transgenics, the volume of interstitial collagen associated with airway wall was significantly less. In intrapulmonary blood vessels, collagen was 8.9% of the wall in transgenics and 0.7% of the wall in non-transgenics. Since blood vessels were a smaller percentage of the lungs in transgenics, the volume of collagen associated with the walls of blood vessels was five times greater. In the lung parenchyma, collagen was 51.5% of the tissue volume in transgenics and 21.2% in non-transgenics. Since parenchyma was a larger percentage of lung volume in transgenics, but the parenchymal tissue was a smaller percent of the volume, the volume of collagen associated with parenchymal tissue was only slightly greater. We conclude that overexpression of TGF-α during lung maturation alters many aspects of lung development, including branching morphogenesis of the airways and vessels and alveolarization in the parenchyma. Further, the increases in visible collagen previously associated with pulmonary fibrosis due to the overexpression of TGF-α are a result of actual increases in amounts of collagen and in a redistribution of collagen within compartments which results from morphogenetic changes. These morphogenetic changes vary by lung compartment. Supported by HL20748, ES06700 and the Cystic Fibrosis Foundation.

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