Delayed Microvascular Shear Adaptation in Pulmonary Arterial Hypertension. Role of Platelet Endothelial Cell Adhesion Molecule-1 Cleavage

Szulcek, Robert; Happé, Chris; Rol, Nina; Fontijn, Ruud D.; Dickhoff, Chris; Hartemink, Koen J.; Grünberg, Katrien; Tu, Ly; Timens, Wim; Nossent, George; Paul, Marinus A.; Leyen, Thomas A.; Horrevoets, Anton J.G.; Man, Frances S. de; Guignabert, Christophe; Yu, Paul B.; Vonk‐Noordegraaf, Anton; Amerongen, Geerten P. van Nieuw; Bogaard, Harm Jan

doi:10.1164/rccm.201506-1231oc

Cited by 80 publications

(68 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Pulmonary vascular remodeling, including changes in the large proximal vessels, has been associated with the PAH pathobiology, that may be related to increased inflammation due to increased hemodynamic stress 2,23,24 . While PAH-associated inflammatory processes have been previously associated with pulmonary vascular remodeling, changes in tissue remodeling in the aorta has not been examined.…”

Section: Discussionmentioning

confidence: 99%

Apparent Aortic Stiffness in Children With Pulmonary Arterial Hypertension

Schäfer

Ivy

Barker

et al. 2017

Circ: Cardiovascular Imaging

View full text Add to dashboard Cite

Background Left ventricular (LV) dysfunction, mediated by ventricular interdependence, has been associated with negative outcomes in children with pulmonary arterial hypertension (PAH). Considering the dilation of the pulmonary arteries as a paramount sign of PAH, we hypothesized that the ascending aorta will present signs of apparent stiffness in children with PAH, and that this effect may be due to mechanical interaction with the dilated main pulmonary artery (MPA). Methods and Results 42 children with PAH and 26 age- and size-matched controls underwent comprehensive CMR evaluation. Assessment of aortic stiffness was evaluated by measuring pulse wave velocity (PWV), aortic strain, and distensibility. Children with PAH had significantly increased PWV in the ascending aorta (3.4 vs. 2.3 m/s for PAH and controls, respectively; p = 0.001), and reduced aortic strain (23 vs. 29%, p < 0.0001) and distensibility (0.47 vs. 0.64 %/mmHg, p = 0.02). Indexed MPA diameter correlated with PWV (p = 0.04) and with aortic strain (p = 0.02). The ratio of MPA to aortic size correlated with PWV (p = 0.0098), strain (p = 0.0099), and distensibility (p = 0.015). Furthermore, aortic relative area change was associated with LV ejection fraction (p = 0.045) and ventricular-vascular coupling ratio (p = 0.042). Conclusions Pediatric PAH patients have increased apparent ascending aortic stiffness, which was strongly associated with the degree of MPA distension. We speculate that distension of the MPA may play a major role in limiting full aortic expansion during systole, which modulates LV performance and impacts systemic hemodynamics in pediatric PAH.

show abstract

Section: Discussionmentioning

confidence: 99%

Apparent Aortic Stiffness in Children With Pulmonary Arterial Hypertension

Schäfer

Ivy

Barker

et al. 2017

Circ: Cardiovascular Imaging

View full text Add to dashboard Cite

show abstract

“…Similarly, in vitro steady shear stress flow patterns could be generated by various types of dedicated apparatus to deliver a specific, unidirectional, and constant flow rate across a cultured endothelial monolayer in a geometrically uniform flow chamber. Various levels of shear stress could be applied to pulmonary microvascular endothelial cell monolayers, ranging from physiological (2.5 dyn/cm 2 ) to high shear (15 or ultimately 21 dyn/cm 2 ), and maintained up to 72 hours or increased gradually with various flow profiles at intervals of 24 hours (37,38). Finally, the availability of coculture technology could also be useful when answering specific biological questions and for studying both physiological and pathophysiological interactions between different cell populations (e.g., immune cells with PASMCs) (39).…”

Section: Lessons From Conventional Two-dimensional Culture Systems Tomentioning

confidence: 99%

Translating Research into Improved Patient Care in Pulmonary Arterial Hypertension

Bonnet

Provencher

Guignabert

et al. 2017

Am J Respir Crit Care Med

Self Cite

114

View full text Add to dashboard Cite

“…2) [10]. Die ausgeprägten Schwankungen des arteriellen Drucks, die mit der Sympathikus-Überstimulation bei OSA-Patienten einhergehen, führen zu vermehrten Scherkräften in den Gefäßen und zur Endotheldysfunktion [35,36,37]. Wiederholte Hypoxien und Reoxygenierungen können Hypoxie-induzierbare Faktoren, den vaskulären endothelialen Wachstumsfaktor und Erythropoetin hochregulieren und Entzündungsprozesse anstoßen [38].…”

Section: Mechanismen Die Präkapilläre Ph Und Sbas Verbindenunclassified

Präkapilläre pulmonale Hypertonie und schlafbezogene Atmungsstörungen: Gibt es einen Zusammenhang?

2018

View full text Add to dashboard Cite

Zur Prävalenz der präkapillären pulmonalen Hypertonie (PH) bei Patienten mit Schlafapnoe liegen sehr unterschiedliche Angaben vor, je nach Auswahl der Patienten, Krankheitsdefinition und Begleiterkrankungen, insbesondere chronische Lungenerkrankungen. Wenn keine Komorbiditäten vorliegen, scheint PH bei Patienten mit Schlafapnoe jedoch selten zu sein. Umgekehrt kommen schlafbezogene Atmungsstörungen bei PH-Patienten häufig vor und gehen mit einer Beeinträchtigung ihrer Lebensqualität einher. Da sich schlafbezogene Atmungsstörungen auf den Lungenkreislauf auswirken können und umgekehrt, sollten Patienten mit schlafbezogenen Atmungsstörungen auf Risikofaktoren, Symptome und klinische Anzeichen für PH und rechtsventrikuläre Herzinsuffizienz untersucht werden, und Patienten mit PH sollten im Hinblick auf Schlafapnoe evaluiert werden. Mögliche Therapieoptionen für Patienten mit Schlafapnoe und PH sind zum Beispiel Sauerstoffgabe, Medikamente und Überdruckbeatmung. Sowohl nächtliche Sauerstoffgabe als auch Acetazolamid bewirken nachweislich eine Besserung der Schlafapnoe bei PH-Patienten. Eine Sauerstofftherapie verbesserte außerdem die körperliche Belastbarkeit. Weitere Studien sind erforderlich, um die Wirksamkeit dieser und anderer Behandlungsmaßnahmen zu unterfüttern. Übersetzung aus Respiration 2017;93:65-77 (DOI: 10.1159/000452957)

show abstract

Delayed Microvascular Shear Adaptation in Pulmonary Arterial Hypertension. Role of Platelet Endothelial Cell Adhesion Molecule-1 Cleavage

Abstract: Delayed shear adaptation, which promotes shear-induced endothelial injury, is a newly identified dysfunction specific to the microvascular endothelium in PAH. The shear response is normalized on stabilization of PECAM-1, which reverses intimal remodeling in vivo.

Cited by 80 publications

References 41 publications

Apparent Aortic Stiffness in Children With Pulmonary Arterial Hypertension

Apparent Aortic Stiffness in Children With Pulmonary Arterial Hypertension

Translating Research into Improved Patient Care in Pulmonary Arterial Hypertension

Präkapilläre pulmonale Hypertonie und schlafbezogene Atmungsstörungen: Gibt es einen Zusammenhang?

Contact Info

Product

Resources

About