Human lung vascular endothelium may limit viral replication and recover in time upon the infection with rhinovirus <scp>HRV16</scp>

Likońska, Aleksandra; Gawrysiak, Mateusz; Gajewski, Adrian; Klimczak, Kinga; Michlewska, Sylwia; Szewczyk, Robert; Gulbas, Izabela; Chałubiński, Maciej

doi:10.1111/apm.13269

Cited by 3 publications

(3 citation statements)

References 19 publications

(25 reference statements)

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“…Lung-derived human microvascular endothelial cells (HMVEC-Ls) demonstrated distinct loss of endothelial barrier integrity resulting in depleted cadherin expression and induced permeability after RV-A16 exposure. This may be associated with increased apoptosis that was also observed or possibly broad dysfunction of the endothelium that transiently prevented proliferative and migratory capacity of exposed cells [ 162 , 163 ]. Vascular permeability in response to RV exposure may enable trans-endothelial migration of circulating immune cells into airway-adjacent tissue and may exaggerate airway inflammation [ 164 ].…”

Section: Structural Cells Of the Airwaymentioning

confidence: 99%

“…Upon RV exposure, HMVEC-Ls also produced strong inflammatory responses, including Th2 cytokines IL-4 and IL-13, that may promote remodeling cascades within lung microvasculature or other airway structural cells [ 161 ]. Notably, direct infection of HMVEC-Ls induced the upregulation of VEGFA , ANGPT1 (angiopoietin-1), and FGF2 gene expression, as well as upregulation of VEGF receptor genes FLT1 , KDR , and NRP1 [ 163 ]. Importantly, the upregulation of both proangiogenic mediators and receptors in HMVEC-Ls may enable a feed-forward signaling loop that promotes endothelial remodeling and neovascularization near airways.…”

Section: Structural Cells Of the Airwaymentioning

confidence: 99%

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Rhinovirus induces airway remodeling: what are the physiological consequences?

Spector,

De Sanctis,

Panettieri

et al. 2023

Respir Res

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Background Rhinovirus infections commonly evoke asthma exacerbations in children and adults. Recurrent asthma exacerbations are associated with injury-repair responses in the airways that collectively contribute to airway remodeling. The physiological consequences of airway remodeling can manifest as irreversible airway obstruction and diminished responsiveness to bronchodilators. Structural cells of the airway, including epithelial cells, smooth muscle, fibroblasts, myofibroblasts, and adjacent lung vascular endothelial cells represent an understudied and emerging source of cellular and extracellular soluble mediators and matrix components that contribute to airway remodeling in a rhinovirus-evoked inflammatory environment. Main body While mechanistic pathways associated with rhinovirus-induced airway remodeling are still not fully characterized, infected airway epithelial cells robustly produce type 2 cytokines and chemokines, as well as pro-angiogenic and fibroblast activating factors that act in a paracrine manner on neighboring airway cells to stimulate remodeling responses. Morphological transformation of structural cells in response to rhinovirus promotes remodeling phenotypes including induction of mucus hypersecretion, epithelial-to-mesenchymal transition, and fibroblast-to-myofibroblast transdifferentiation. Rhinovirus exposure elicits airway hyperresponsiveness contributing to irreversible airway obstruction. This obstruction can occur as a consequence of sub-epithelial thickening mediated by smooth muscle migration and myofibroblast activity, or through independent mechanisms mediated by modulation of the β2 agonist receptor activation and its responsiveness to bronchodilators. Differential cellular responses emerge in response to rhinovirus infection that predispose asthmatic individuals to persistent signatures of airway remodeling, including exaggerated type 2 inflammation, enhanced extracellular matrix deposition, and robust production of pro-angiogenic mediators. Conclusions Few therapies address symptoms of rhinovirus-induced airway remodeling, though understanding the contribution of structural cells to these processes may elucidate future translational targets to alleviate symptoms of rhinovirus-induced exacerbations.

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Section: Structural Cells Of the Airwaymentioning

confidence: 99%

Section: Structural Cells Of the Airwaymentioning

confidence: 99%

Rhinovirus induces airway remodeling: what are the physiological consequences?

Spector,

De Sanctis,

Panettieri

et al. 2023

Respir Res

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“…In our previous studies, we have shown that rhinovirus HRV16 infection of the human lung vascular endothelium induced a strong inflammatory cytokine and Type I and III IFN synthesis accompanied by an upregulation of OAS‐1 and PKR mRNA expression [2, 4]. We also proved the ability of HRV16‐infected endothelium to restore and gain its barrier capacities [8]. OAS‐1 and PKR are IFN‐dependent agents that may be directly involved in the inhibition of viral replication by degrading viral RNA and suppressing the translation of major structural viral proteins, such as capsid proteins.…”

mentioning

confidence: 99%

Human lung vascular endothelium may limit infection with HRV16viaIFN‐β‐dependent mechanisms

Gawrysiak,

Szewczyk,

Kobierecki

et al. 2023

APMIS

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Human rhinovirus 16 (HRV16) may induce inflammatory and antiviral responses in the human lung vascular endothelium (ECs) and impair its barrier functions after infection. However, ECs may regain barrier and metabolic functions. Mechanisms of limitation of HRV16 infection in the lung vascular endothelium are unknown. Human lung vascular endothelium (HMVEC‐L) was infected with HRV16. IFN‐β, OAS‐1, and PKR expression was assessed by real‐time PCR, flow cytometry, and confocal microscope. To prove the significance of IFN‐β in the limitation of HRV16 replication, HMVEC‐Ls were preincubated with anti‐IFN‐β Abs. To prove the involvement of OAS‐1 and PKR in the IFN‐dependent limitation of HRV16 replication, HMVEC‐Ls were transfected with respective siRNA. HRV16 stimulated IFN‐β production and activated intracellular mechanisms of antiviral immunity based on OAS‐1 and PKR activation. Blocking of IFN‐β contributed to the inhibition of intracellular mechanisms of antiviral immunity (OAS‐1, PKR) and boosted replication of HRV16. Effective OAS‐1 silencing by siRNA caused the increase of HRV16 copy numbers after HRV16 infection. siRNA upregulated the other genes related to the antiviral response. The infected lung vascular endothelium may limit the HRV16 infection. This limitation may be associated with the induction of IFN‐β‐dependent intracellular mechanisms based on OAS‐1 and PKR activity.

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Respiratory viruses and postoperative hemodynamics in patients with unrestrictive congenital cardiac communications: a prospective cohort study

et al. 2023

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Background Pulmonary vascular abnormalities pose a risk for severe life-threatening hemodynamic disturbances following surgical repair of congenital cardiac communications (CCCs). In the distal lung, small airways and vessels share a common microenvironment, where biological crosstalks take place. Because respiratory cells infected by viruses express a number of molecules with potential impact on airway and vascular remodeling, we decided to test the hypothesis that CCC patients carrying viral genomes in the airways might be at a higher risk for pulmonary (and systemic) hemodynamic disturbances postoperatively. Methods Sixty patients were prospectively enrolled (age 11 [7–16] months, median with interquartile range). Preoperative pulmonary/systemic mean arterial pressure ratio (PAP/SAP) was 0.78 (0.63–0.88). The presence or absence of genetic material for respiratory viruses in nasopharyngeal and tracheal aspirates was investigated preoperatively in the absence of respiratory symptoms using real-time polymerase chain reaction (kit for detection of 19 pathogens). Post-cardiopulmonary bypass (CPB) inflammatory reaction was analyzed by measuring serum levels of 36 inflammatory proteins (immunoblotting) 4 h after its termination. Postoperative hemodynamics was assessed using continuous recording of PAP and SAP with calculation of PAP/SAP ratio. Results Viral genomes were detected in nasopharynx and the trachea in 64% and 38% of patients, respectively. Rhinovirus was the most prevalent agent. The presence of viral genomes in the trachea was associated with an upward shift of postoperative PAP curve (p = 0.011) with a PAP/SAP of 0.44 (0.36–0.50) in patients who were positive versus 0.34 (0.30–0.45) in those who were negative (p = 0.008). The presence or absence of viral genomes in nasopharynx did not help predict postoperative hemodynamics. Postoperative PAP/SAP was positively correlated with post-CPB levels of interleukin-1 receptor antagonist (p = 0.026), macrophage migration inhibitory factor (p = 0.019) and monocyte chemoattractant protein-1 (p = 0.031), particularly in patients with virus-positive tracheal aspirates. Conclusions Patients with CCCs carrying respiratory viral genomes in lower airways are at a higher risk for postoperative pulmonary hypertension, thus deserving special attention and care. Preoperative exposure to respiratory viruses and post-CPB inflammatory reaction seem to play a combined role in determining the postoperative behavior of the pulmonary circulation.

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Human lung vascular endothelium may limit viral replication and recover in time upon the infection with rhinovirus HRV16

Cited by 3 publications

References 19 publications

Rhinovirus induces airway remodeling: what are the physiological consequences?

Rhinovirus induces airway remodeling: what are the physiological consequences?

Human lung vascular endothelium may limit infection with HRV16viaIFN‐β‐dependent mechanisms

Respiratory viruses and postoperative hemodynamics in patients with unrestrictive congenital cardiac communications: a prospective cohort study

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