Fig 1.
Aortic root dimension of WT and MFS mice.
(A) B-mode view of the aortic arch from a 6-month MFS mouse. Diameters of the (B) aortic annulus [L1], (C) sinus of Valsalva [L2] and (D) sinotubular junction [L3] were significantly increased in MFS mice versus WT. The larger aortic root diameter indicates significant aortic dilation. * indicates p < 0.05, ** indicates p< 0.01, *** indicates p< 0.001. (n = 8)
Fig 2.
Pulse wave velocity (PWV) of aortic arch.
(A) B-mode view of aortic arch of a 6-month wild type (WT) mouse. The distance between the ascending and descending aorta pulse wave Doppler recordings is indicated by the blue line (d0 to d). Scale bars, 2 mm. (B) Pulse wave Doppler tracing of the ascending (upper panel) and descending aorta (lower panel). The X-axis represents time (ms) and Y-axis represents blood flow velocity (mm/s). T1 is measured from the beginning of the QRS wave on the ECG to the beginning of the ascending aortic peak velocity and T2 is the beginning of the QRS wave on the ECG to the beginning of the descending aortic peak velocity. Pulse wave velocity was calculated using the distance between d0 and d in the aortic arch divided by the transit time (i.e. [d-d0] / [T2-T1]). (C) Aortic PWV of WT and MFS mice from two age groups (6–8 months and 12–16 months group). PWV was significantly increased in 6–8 months MFS mice compared to WT (p = 0.003) and in 12–16 months MFS mice compared to WT (p< 0.001), respectively. (D) Correlations between age (x-axis) and PWV (y-axis) of WT (●) and MFS (■) mice. PWV in MFS mice was directly proportional to age (R-squared = 0.356, p = 0.02), but not in WT mice. ** indicates p< 0.01, *** indicates p< 0.001. (n = 8)
Table 1.
Echocardiographic functional analysis for WT and MFS mice.
Fig 3.
Peak velocity was calculated from pulsed-wave Doppler mode from an aortic arch view.
(A) Ascending aortic peak velocity of WT and MFS mice from two age groups (6- and 12-month). Ascending aortic peak velocity was significantly decreased in 12-month MFS mice versus WT mice (p = 0.04). (B) Descending aortic peak velocity was significantly decreased in 12-month MFS mice (p< 0.001) versus WT mice. * indicates p< 0.05, *** indicates p< 0.001. (n = 8)
Fig 4.
Echocardiographic assessment of left ventricle (LV) mass and wall thickness.
Left ventricle (LV) mass, systolic and diastolic wall thickness were normalized by body weight (g). Data presented are normalized systolic and diastolic (A) anterior wall thickness, (B) posterior wall thickness, (C) interventricular septal thickness and (D) normalized LV mass from WT and MFS mice (n = 8). * indicates p< 0.05.
Fig 5.
Mitral inflow velocity of WT and MFS mice.
(A) Mitral inflow velocity profile of WT (left panel) and MFS (right panel) mice at 6 months. Velocity (mm/s, y-axis) is shown as a function of time (ms, x-axis). Mitral valve early peak (MV E) velocity was determined from the first peak and atrial peak velocity (MV A) from the second peak. Isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT) and ejection time (ET) are displayed in blue and red lines, respectively. (B) MV E velocity, (C) MV A velocity, (D) E/A ratio, (E) IVRT, (F) ET and (G) Myocardial performance index (MPI) were measured from WT and MFS mice (n = 8). * indicates p< 0.05, ** indicates p< 0.01, *** indicates p< 0.001.
Fig 6.
Histological analysis of WT and MFS mice aorta.
(A) Representative histological images stained with Van Gieson's staining reveal the arrangement of elastin (dark blue) and collagen (pink) in the cross-section of the aorta from 6-month and 12-month wild-type (WT) and Marfan (MFS) mice. Elastin fibers display severe fragmentation and disorganization in the MFS aorta as compared with WT samples. (B) The area and (C) number of elastin fibers were measured by tracing the elastin fibers on the transverse section of mouse aorta. * indicates p< 0.05 (n = 3).
Fig 7.
Representative 3D high-resolution volumetric OCT data set.
(A) Volumetric rendering of representative OCT data set acquired from a MFS mouse. (B) Cross-sectional view at the plane indicated by the black box in (A). Scale bar denotes 2 mm.
Table 2.
Structural properties of 12-month-old WT and MFS Mice in OCT study.
Fig 8.
Comparison of the 2D and 3D LV volume measurements from the OCT data set. Comparison of the LV volume, as determined by the Teichholz method based on 2D measurements on the OCT data, and by direct volume measurement from the 3D OCT data set.
(A) The diameter of the lumen was measured from the short-axis slice located at the mid-papillary level, from the anterior to posterior wall, as shown by the dashed white line. The volume was estimated from the diameter measurement using Teicholz’s equation. Scale bar denotes 2 mm. (B) The ratio of the estimated volume (using Teichholz method) to measured volume (computed in 3D) was significantly different between the WT and MFS mice (p< 0.01). (C) Linear regression on the estimated volume (in 2D) and actual volume (computed in 3D). The LV volumes of the MFS mice are overestimated in the 2D estimation formula by up to 40% (WT, n = 4; MFS, n = 7). ** indicates p< 0.01.