Patients with mutant gene encoding type III collagen experience arterial ruptures, called vascular Ehlers-Danlos syndrome (vEDS). Our goal was to assess the aortic mechanical behaviour by measuring the pulse wave velocity (PWV) at different blood pressure levels in the new model of vEDS: Knock-In Gly183Arg mice (col3KI-mice) presenting a qualitative default in type III collagen.

We compared Black-6 col3KI-mice to their wild type (WT) littermates. An age of 12–20 weeks was chosen, due to high early mortality rate in col3KI-mice. Doses of phenylephrine (0.01–700 μg/kg) were used to increase the blood pressure, recorded with a carotid catheter in anesthetized mice. Abdominal aortic PWV was measured by Ultrafast ultrasound imaging (2800 frames/s) with a 15 MHz probe. PWV was measured at the waveform's foot (PWV1), generated at the minimal diastolic blood pressure (DBP) and at the dicrotic notch (PWV2), at the systolic blood pressure (SBP). To evaluate the arterial intrinsic properties, we reported each PWV to their corresponding arterial pressure: PWV1/DBP and PWV2/SBP. Difference of these two PWV (Delta-PWV), reported to the pulse pressure (PP) as Delta-PWV/PP, is related to the arterial stiffening in the cardiac cycle. Mann-Whitney test was used for comparisons.

8 col3KI-mice (5 females, 3 males) were compared to 23 WT (12 females, 11 males) of comparable age (124±28 days) and weight (25.7±4.3g). PWV1/DBP was lower in col3KI-mice (2.73 cm.s⁻¹.mmHg⁻¹ [2.61–2.85] vs. 2.99 [2.89–3.09]; P=0.027). This was also the case at the systolic level, with lower PWV2/SBP (2.86 [2.75–2.98] vs. 3.61 [3.48–3.74]; P<10⁻¹⁵). Delta-PWV/PP (cm.s⁻¹.mmHg⁻¹) was lower in col3KI mice (4.38 [3.56–5.18] vs. 8.12 [6.98–9.27]; P<10⁻⁶) showing a lack of stiffening during the cardiac cycle (Fig. 1).

In col3KI-mice, arterial rupture may be underlain by the lack of arterial stiffening due to the absence of type III collagen recruitment when pressure rises.