Figure 4. TSP-1 loss in db/db mice results in dilative cardiac remodeling and decreased left ventricular wall thickness.

Echocardiographic imaging showed that db/db TSP-1 null mice (dbTSP) had increased Left Ventricular End-Diastolic Diameter (LVEDD) (A) and Left Ventricular End-Diastolic Volume (LVEDV) (B) when compared with db/db animals (db), suggesting increased dilative remodeling (*p<0.05, **p<0.01 vs. age-matched db/db mice; db/db, n=14; dbTSP, n=19). C. At 4 months of age, systolic function was mildly depressed in dbTSP mice; however, loss of TSP-1 did not cause prolonged or progressive systolic ventricular dysfunction. D–F. TSP-1 absence in db/db animals attenuated cardiac hypertrophy leading to reductions in left ventricular mass (D), anterior wall end-diastolic thickness (AWT, E) and posterior wall end-diastolic thickness (PWT, F). G. At 6 months of age, db/db mice had significantly increased left atrial area when compared with WT animals (**p<0.01). TSP-1 loss significantly abrogated the increase in LA size observed in diabetic animals H. Mitral inflow Doppler echocardiography showed that db/db animal had a significant reduction in the E:A ratio suggesting impaired relaxation (*p<0.05 vs. WT). TSP-1 loss did not affect the E:A ratio in lean or obese mice. I–L. Assessment of left ventricular contractile reserve in a Langendorff model demonstrated that at 6 months of age, obese diabetic db/db mice and WT lean animals had no difference in systolic function, assessed through measurements of dp/dtmax (I) and LVDP (J), both at baseline and after infusion of dobutamine. TSP-1 loss did not significantly affect systolic function in db/db mice; only trends towards reduced LVDP and dp/dtmax were observed with low-dose dobutamine infusion. However, TSP-1 loss in db/db mice significantly delayed the peak systolic response after dobutamine infusion (K). L. Diastolic function, measured through assessment of −dp/dtmin was not significantly affected by TSP-1 loss (**p<0.01 vs. baseline −dp/dtmin).