The role of endothelial leak in pulmonary hypertension (2017 Grover Conference Series)

Zhou, Chun; Francis, C.M.; Xu, Ningyong; Stevens, Troy

doi:10.1177/2045894018798569

Cited by 7 publications

(2 citation statements)

References 48 publications

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“…We were more likely to obtain viable PAECs from PAH patients with more severe disease (as evidenced by hemodynamics and possibly shorter 6MWD), which in part may be related to our observation that PAH PAECS were more apoptosis resistant compared to commercial PAECs. Altered mechanical properties (i.e., hyperpermeability) of PAH PAECs may have lead to increased transfer from the endothelium to the PAC balloon, as has been shown in experimental PH (13). These observations are preliminary and require confirmation.…”

Section: Discussionmentioning

confidence: 83%

Culture of pulmonary artery endothelial cells from pulmonary artery catheter balloon tips: considerations for use in pulmonary vascular disease

et al. 2020

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Endothelial dysfunction is a hallmark of pulmonary arterial hypertension (PAH) but there are no established methods to study pulmonary artery endothelial cells (PAECs) from living patients. We sought to culture PAECs from pulmonary artery catheter (PAC) balloons used during right-heart catheterisation (RHC) to characterise successful culture attempts and to describe PAEC behaviour.PAECs were grown in primary culture to confluence and endothelial cell phenotype was confirmed. Standard assays for apoptosis, migration and tube formation were performed between passages three to eight. We collected 49 PAC tips from 45 subjects with successful PAEC culture from 19 balloons (39%).There were no differences in subject demographic details or RHC procedural details in successful versus unsuccessful attempts. However, for subjects who met haemodynamic criteria for PAH, there was a higher but nonsignificant (p=0.10) proportion amongst successful attempts (10 out of 19, 53%) versus unsuccessful attempts (nine out of 30, 30%). A successful culture was more likely in subjects with a lower cardiac index (p=0.03) and higher pulmonary vascular resistance (p=0.04). PAECs from a subject with idiopathic PAH were apoptosis resistant compared to commercial PAECs (p=0.04) and had reduced migration compared to PAECs from a subject with portopulmonary hypertension with high cardiac output (p=0.01). PAECs from a subject with HIV-associated PAH formed fewer (p=0.01) and shorter (p=0.02) vessel networks compared to commercial PAECs.Sustained culture and characterisation of PAECs from RHC balloons is feasible, especially in PAH with high haemodynamic burden. This technique may provide insight into endothelial dysfunction during PAH pathogenesis.

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Section: Discussionmentioning

confidence: 83%

Culture of pulmonary artery endothelial cells from pulmonary artery catheter balloon tips: considerations for use in pulmonary vascular disease

et al. 2020

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“…The role of TRPC4 in PAH was investigated in a model of hypoxic PAH in which rats were pretreated with a vascular endothelial growth factor receptor 2 inhibitor, exposed to three weeks of hypoxia, and then returned to normoxia. In this model, TRPC4 contributed to the hyper-permeability of endothelial cells, demonstrating a novel type of endothelial abnormality in severe experimental PAH [ 168 ].…”

Section: Trp Channels and The Development Of Pulmonary Arterial Hyper...mentioning

confidence: 99%

Transient Receptor Potential (TRP) Channels in Airway Toxicity and Disease: An Update

Müller¹,

Alt²,

Rajan³

et al. 2022

Cells

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Our respiratory system is exposed to toxicants and pathogens from both sides: the airways and the vasculature. While tracheal, bronchial and alveolar epithelial cells form a natural barrier in the airways, endothelial cells protect the lung from perfused toxic compounds, particulate matter and invading microorganism in the vascular system. Damages induce inflammation by our immune response and wound healing by (myo)fibroblast proliferation. Members of the transient receptor potential (TRP) superfamily of ion channel are expressed in many cells of the respiratory tract and serve multiple functions in physiology and pathophysiology. TRP expression patterns in non-neuronal cells with a focus on TRPA1, TRPC6, TRPM2, TRPM5, TRPM7, TRPV2, TRPV4 and TRPV6 channels are presented, and their roles in barrier function, immune regulation and phagocytosis are summarized. Moreover, TRP channels as future pharmacological targets in chronic obstructive pulmonary disease (COPD), asthma, cystic and pulmonary fibrosis as well as lung edema are discussed.

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Pulmonary Circulation in Obesity, Diabetes, and Metabolic Syndrome

Khaing

Pandit

Awsare

et al. 2019

Comprehensive Physiology

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Obesity, diabetes mellitus, and the metabolic syndrome are important risk factors for the development of cardiovascular disease, with significant impact on human morbidity and mortality. Several decades of research have accumulated considerable knowledge about the mechanisms by which metabolic conditions precipitate systemic cardiovascular diseases. In short, these mechanisms are thought to involve changes in the external environment of vascular cells, which are mediated by the pro-inflammatory effects of adipokines, free fatty acids, and hyperglycemia. Thus, it has been hypothesized that the pulmonary circulation, witnessing similar insults as the systemic circulation, may be equally vulnerable to the development of vascular disease. Accordingly, recent attention has focused on exploring the mechanistic and epidemiological relationships among obesity, type 2 diabetes mellitus, metabolic syndrome, and pulmonary vascular diseases. In this article, we discuss in detail the preclinical evidence showing a modest but perceivable impact of metabolic disorders on the pulmonary circulation. In addition, we review the existing epidemiological studies examining the relationship among cardiovascular risk factors and pulmonary vascular diseases, using the acute respiratory distress syndrome and pulmonary arterial hypertension as examples. We conclude by discussing areas of limitations in the field and by suggesting future directions for investigation, including the notion that the pulmonary circulation may, in fact, be a resilient entity in the setting of some metabolic perturbations.

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The role of endothelial leak in pulmonary hypertension (2017 Grover Conference Series)

Cited by 7 publications

References 48 publications

Culture of pulmonary artery endothelial cells from pulmonary artery catheter balloon tips: considerations for use in pulmonary vascular disease

Culture of pulmonary artery endothelial cells from pulmonary artery catheter balloon tips: considerations for use in pulmonary vascular disease

Transient Receptor Potential (TRP) Channels in Airway Toxicity and Disease: An Update

Pulmonary Circulation in Obesity, Diabetes, and Metabolic Syndrome

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