Abstract 16342: Cardiac Specific Heat Shock Protein B2 (HSPB2) Exerts Paradoxical Cardioprotection Against Pressure Overload and Ischemic/Reperfusion in Mice
Backgrounds and Objectives Small Heat Shock Proteins (HSPs) display chaperone-like activities and protect cells against apoptosis and ischemia/reperfusion (I/R) injury. HSPB2 is expressed at high levels in skeletal muscle and the heart, localizes on the outer mitochondrial membrane and the neuromuscular junction, binds to dystrophy myosin kinase protein (DMPK). For the adjacently arranged CryAB and HSPB2 at genomic level, we previously reported that double knockout paradoxically protects the heart after I/R ex vivo and in vivo. We hypothesized that the absence of HSPB2 would protect the heart against pressure overload and I/R.
Methods To test this hypothesis, we generated cardiac-specific HSPB2 knockout mice (B2KO) and investigated cardiac phenotypes at baseline and under conditions of pressure overload (TAC: Trans-aortic banding) for 4 weeks or I/R using Langendorff system (i.e, ischemia 30 min/reperfusion 45 min). Standard methods after TAC for cardiac hypertrophy, left ventricle hemodynamics, I/R injury, and mitochondrial respiration were employed.
Results Four weeks after TAC, the survival rate of B2KO was improved compared with controls (83.3% in B2KO (n=12) vs. 69.2% in control (n=13)). There were no significant differences in hypertrophy, left ventricle hemodynamics, including heart rate, systolic pressure, and end-diastolic pressure between B2KO and control at 4 weeks after TAC. Likewise, we observed post-ischemic LV systolic pressure was higher in B2KO compared with control (80.6 ± 34.8 mmHg in B2KO (n=11) vs. 60.6 ± 17.4 mmHg in control (n=10), p<0.05). And the mitochondrial respiration rates were indistinguishable between B2KO and control, at baseline after cardiac stress.
Conclusion In conclusion, HSPB2 deficiency abrogates adverse ventricular remodeling after pressure overload and ischemia-induced injury, suggesting novel mechanism(s) for cardiac viability. Ongoing studies are testing the intriguing hypothesis that HSPB2 interacts with its binding partner DMPK functional integrity and membrane permeability.
- © 2011 by American Heart Association, Inc.