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Ultraschall Med 2019; 40(06): 734-742
DOI: 10.1055/a-0599-0841
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Arterial Stiffening with Ultrafast Ultrasound Imaging Gives New Insight into Arterial Phenotype of Vascular Ehlers-Danlos Mouse Models

Arterielle Steifigkeit mittels Ultrafast-US-Imaging gibt neuen Einblick in den arteriellen Phänotyp von vaskulären Ehlers-Danlos-Mausmodellen
Guillaume Goudot
1   Institut Langevin, INSERM U979, CNRS UMR 7587, ESPCI Paris, PSL Research University, Paris France
3   USPC Sorbonne Paris Cité, Paris Descartes University, Paris, France
,
Clément Papadacci
1   Institut Langevin, INSERM U979, CNRS UMR 7587, ESPCI Paris, PSL Research University, Paris France
,
Blandine Dizier
2   INSERM UMR_S1140, Faculté de Pharmacie, Paris, France
3   USPC Sorbonne Paris Cité, Paris Descartes University, Paris, France
,
Véronique Baudrie
3   USPC Sorbonne Paris Cité, Paris Descartes University, Paris, France
4   PARCC, INSERM U970, Paris, France
,
Irmine Ferreira
3   USPC Sorbonne Paris Cité, Paris Descartes University, Paris, France
4   PARCC, INSERM U970, Paris, France
,
Catherine Boisson-Vidal
2   INSERM UMR_S1140, Faculté de Pharmacie, Paris, France
3   USPC Sorbonne Paris Cité, Paris Descartes University, Paris, France
,
Mickaël Tanter
1   Institut Langevin, INSERM U979, CNRS UMR 7587, ESPCI Paris, PSL Research University, Paris France
,
Xavier Jeunemaître
3   USPC Sorbonne Paris Cité, Paris Descartes University, Paris, France
4   PARCC, INSERM U970, Paris, France
5   Hôpital Européen Georges-Pompidou, Assistance Publique – Hôpitaux de Paris, France
,
Mathieu Pernot
1   Institut Langevin, INSERM U979, CNRS UMR 7587, ESPCI Paris, PSL Research University, Paris France
,
Emmanuel Messas
3   USPC Sorbonne Paris Cité, Paris Descartes University, Paris, France
4   PARCC, INSERM U970, Paris, France
5   Hôpital Européen Georges-Pompidou, Assistance Publique – Hôpitaux de Paris, France
,
Tristan Mirault
3   USPC Sorbonne Paris Cité, Paris Descartes University, Paris, France
4   PARCC, INSERM U970, Paris, France
5   Hôpital Européen Georges-Pompidou, Assistance Publique – Hôpitaux de Paris, France
› Author Affiliations
Further Information

Publication History

07 August 2017

08 March 2018

Publication Date:
21 September 2018 (online)

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Abstract

Objective Vascular Ehlers–Danlos syndrome (vEDS) is associated with arterial ruptures due to a mutant gene encoding collagen type III (Col-III). To better understand the role of Col-III, we aimed at evaluating aortic stiffness and dynamic stiffening in vEDS mouse models, with either a quantitative (col3KO mice) or a qualitative Col-III defect (col3KI mice).

Materials and Methods Abdominal aortic wall pulse wave velocities (PWV) in col3KO and col3KI mice were compared to their respective wild type (WT) littermates using a 15 MHz ultrafast ultrasonic transducer. A carotid catheter continuously monitored pressure changes due to phenylephrine injections. PWV1, generated at diastolic blood pressure (DBP), and PWV2, at systolic blood pressure (SBP) were recorded. Difference between PWV2 and PWV1 (Delta-PWV) normalized by the pulse pressure (PP), corresponding to the aortic stiffening over the cardiac cycle, were compared between mutant and WT mice, as well as the regression slope of PWV as a function of pressure.

Results Delta-PWV/PP was lower in col3KO (p = 0.033) and col3KI mice (p < 0.001) vs. WT-mice regardless of the pressure level. The slope of PWV1 with DBP increase showed a lower arterial stiffness in mutant mice vs. controls in both models. This difference was amplified when evaluating stiffness at systolic blood pressure levels with PWV2.

Conclusion In both vEDS mouse models, aortic stiffening was reduced, mainly driven by a lower stiffness at systolic blood pressure. Defective Col-III may be responsible for this, as it is utilized when pressure rises. These pre-clinical data could explain vascular fragility observed in vEDS patients.

Zusammenfassung

Ziel Das vaskuläre Ehlers-Danlos-Syndrom (vEDS) ist mit arteriellen Rupturen assoziiert, zurückzuführen auf ein mutiertes Gen, das für Kollagen Typ III (Col-III) kodiert. Um die Rolle von Col-III besser zu verstehen, untersuchten wir die Aortensteifigkeit und die dynamische Steifigkeit in vEDS-Mausmodellen, die entweder einen quantitativen (col3KO-Mäuse) oder einen qualitativen Col-III-Defekt (col3KI-Mäuse) hatten.

Material und Methoden Die Pulswellengeschwindigkeiten der Bauchaortenwand (PWV) in col3KO- und col3KI-Mäusen wurden mit denen ihrer jeweiligen Wildtyp (WT)- Wurfgeschwister mit einem 15 MHz Ultrafast-Ultraschall-Transducer verglichen. Ein Karotiskatheter überwachte fortlaufend die durch Injektion von Phenylephrin hervorgerufenen Druckänderungen. PWV1, erzeugt bei diastolischem Blutdruck (DBP) und PWV2, bei systolischem Blutdruck (SBP) wurden aufgezeichnet. Der Unterschied zwischen PWV2 und PWV1 (Delta-PWV), normalisiert durch den Pulsdruck (PP), welcher der Aortensteifigkeit beim Herzzyklus entspricht, sowie die Regressionsneigung von PWV als Funktion des Drucks wurde zwischen Mutanten- und WT-Mäusen verglichen.

Ergebnisse Delta-PWV/PP war unabhängig vom Druckniveau niedriger in col3KO- (p = 0,033) und col3KI-Mäusen (p < 0,001) im Vergleich zu WT-Mäusen. Die Neigung von PWV1 bei DBP-Anstieg zeigte bei beiden Modellen eine geringere arterielle Steifigkeit in mutierten Mäusen im Vergleich zu den Kontrollen. Dieser Unterschied wurde verstärkt, wenn die Steifigkeit mit PWV2 bei systolischem Blutdruck bewertet wurde.

Schlussfolgerung Beide vEDS-Mausmodelle hatten eine reduzierte Aortensteifigkeit, hauptsächlich durch die geringere Steifigkeit beim systolischen Blutdruck. Das defekte Col-III Gen könnte dafür verantwortlich sein, da es zum Einsatz kommt, wenn der Druck steigt. Diese präklinischen Daten könnten die bei Patienten mit vEDS beobachtete vaskuläre Fragilität erklären.

Key words

aorta - collagen type III - mouse - pulse wave velocity - arterial stiffness

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