Fig. 3

Cardiac phenotyping and vascular remodeling in the DIO + DOCP mouse model. (A) Schematic representation of the DIO + DOCP “two-hit” model. Mice were fed a high-fat diet to induce obesity starting at 6 weeks of age. At 26 weeks, they received a single intraperitoneal injection of deoxycorticosterone pivalate (DOCP, 75 mg/kg) to induce hypertension. Cardiac MRI and echocardiography were performed longitudinally at baseline (before DOCP), 7 days, 14 days, and 1 month after DOCP. (B) No significant difference was observed in arterial pressure and assessment of diastolic function using mitral valve (MV) inflow parameters (E/e’ ratio and deceleration velocity) showed no significant differences between the groups at any time point. (C) No significant differences were observed for LV volumes and LV and RV ejection fractions (EF) between the control, DIO, and DIO + DOCP groups at any time point. LV stroke volume (SV) was significantly increased at baseline in the DIO group compared to the control group (p = 0.05). LV mass was consistently elevated on average in the DIO groups before and after DOCP compared to the control group, although this difference did not reach statistical significance (ns, p = 0.25, ANOVA). Dobutamine injections caused a significant increase in heart rate in all groups. However, both LV end-diastolic and end-systolic volumes tended to decrease, resulting in no significant change in cardiac output compared to rest, suggesting a potential impairment in cardiac contractile reserve. (D) Mid-ventricular myocardial blood flow, measured by cine-ASL, was significantly reduced in both DIO and DIO + DOCP groups compared to controls. Histological analysis confirmed the cine-ASL findings. CD31 staining revealed significantly reduced vessel density in the DIO group. DIO + DOCP hearts also exhibited a trend towards reduced vessel density compared to controls (control group n = 6, DIO group n = 7, DIO + DOCP group n = 8 animals).