Table 1.
Hematologic parameters.
Figure 1.
Longitudinal analysis of body weight in homo-βthal mice at 6, 10 and 14 months.
Homo-βthal mice (filled bars) have significantly decreased body weight relative to controls (open bars) at 10 and 14 months (*p<0.05, **p<0.01). Within the control group, body weight was increased at 10 and 14 months vs 6 months (ap<0.05, bp<0.001), and 14 months vs 10 months (cp<0.05). Values are means±SEM and analyzed by two-way ANOVA.
Table 2.
Organ-to-body ratios of homo-βthal mice.
Figure 2.
Histopathologic analysis of iron deposition in 15-month mouse thalassemic tissues.
Tissue sections were stained for iron deposits with Prussian blue and counterstained with nuclear fast red. A) Spleen of control mice with well-organized white and red pulp displayed mild iron deposits B) Spleen of homo-βthal showed numerous iron deposits throughout the parenchyma. C) Kidney of control mice did not exhibit presence of iron. D) Kidney of homo-βthal mice revealed iron deposits in proximal tubular cells of the cortical region. E) Liver of control mice did not exhibit presence of iron. F) Liver of homo-βthal mice revealed iron deposits in Kupffer cells and in parenchymal cells. (Magnification×20; A-D: bars, 200 µm; E,F: bars, 100 µm).
Figure 3.
Macroscopic and microscopic alterations of murine thalassemic hearts.
Representative cardiac macroscopic phenotype of 15-months control (A) and homo-βthal (B) show important heart hypertrophy in homo-βthal mice; hematoxylin-eosin stain. Heart tissue sections of control (C) in comparison to homo-βthal (D) stained with Sirius red revealed markedly enhanced collagen levels (arrow) in homo-βthal hearts. Histological cardiac analysis of control (E) and homo-βthal (F) sections were comparable with occasional detectable iron signals (arrowhead); Prussian blue stain and nuclear fast red counterstain. (Magnification×40; Bars, 100 µm).
Table 3.
Histopathologic assessment of homo-βthal mice.
Figure 4.
Longitudinal cardiac morphologic analysis of homo-βthal mice.
A) Longitudinal evaluation of LV mass by echocardiography in control (open bars) and homo-βthal mice (filled bars) at ages 6, 10 and 14 months show a progressive increase of LV mass in homo-βthal mice with age. Values are means±SEM. Comparison of LV mass between homo-βthal and control mice (*p<0.05, and **p<0.001) and within homo-βthal mouse groups at 10 vs14 months (†p<0.01) and at 6 vs 14 months († †p<0.001). B) Comparison of echocardiographic measurements at ages 6, 10 and 14 months in homo-βthal (n = 23, 22, 19) and control (n = 18) mice. Cardiac parameters consist of LVDd, left ventricule diameter in diastole; LVDs, left ventricule diameter in systole; IVS, interventricular septum; PW, posterior wall. Values are means±SEM. Cardiac parameters were significantly increased in homo-βthal mice compared to same age controls (*p<0.05, **p<0.01 and ***p<0.001) and within the homo-βthal group, cardiac parameters were increased at 10 and 14 months vs 6 months (†p<0.05 and †† p<0.01). C) Relative wall thickness of homo-βthal (filled bars) relative to control (open bars) mice was consistently diminished at the different analyzed ages 6, 10 and 14 months (*p<0.05 **p<0.01).
Figure 5.
Impaired cardiac function in homo-βthal mice.
A) Longitudinal measurements of cardiac index (CI) in homo-βthal mice (filled bars) at ages 6, 10 and 14 months relative to control (open bars) was increased. B) Mean arterial pressure (MAP) evaluated by tail-cuff approach was comparable in control (open bars) and homo-βthal mice (filled bars). C) Left ventricular ejection fraction (EF) in homo-βthal mice (filled bars) decreased relative to control (open bars) at all ages. D) Left ventricular fractional shortening (FS) in homo-βthal mice (filled bars) declined at 10 and 14 months of age compare to control (open bars). E) Doppler Pourcelot indices (PI, no units) of the common carotid artery in 6, 10 and 14 month-old control (open bars) and homo-βthal mice (filled bars) indicated altered vascular hemodynamics in the homo-βthal mice. Values are means±SEM. *p<0.05, **p<0.01 and †p<0.001 vs. same age control mice.