Question: 

Cardiac hypertrophy depends on focal adhesions that are recruited to the integrin cytoplasmic domains. A complex constituted Ilk, Pinch and the F-actin binding protein parvin (IPP) is crucial for myocard regulation. Capillaries are crucially involved in myocard homeostasis. Disturbed capillary adaptations towards physiological loading result in maladaptive cardiac phenotypes. Stat3 is a potent regulator of capillarization and is regulated by Parvb. It was hypothesized that Parvb-/- leads to pathological cardiac adaptations.

Methodology: 

TAC model was performed on control and Parvb^-/- mice. Mouse echocardiography was performed. Chronic treadmill exercise was performed over 4 wks. Acute treadmill exercise consisted of a single 15min exercise bout at 18m*min-1, angle of 10°. Capillarization was investigated histologically. Total Stat3/Stat3Tyr705 was quantified by WB in control, acute exercised and TAC hearts.

Results: 

No cardiac phenotype in Parvb-/- under resting conditions was observed. Chronic mechanical stimulation resulted in decreased capillarization in Parvb-/- cardiomyocytes. It was observed that acute exercise leads to decreased Stat3Y705 phosphorylation in Parvb-/- hearts compared to WT controls. Capillarization was higher in WT-TAC and Parvb-/--TAC conditions compared to controls. However, no differences in capillarization between WT-TAC and Parvb-/--TAC were observed. Stat3Y705 did not significantly differ between WT-TAC and Parvb-/--TAC hearts, but was higher compared to control conditions.

Conclusion: 

These data support the hypothesis that Parvb-/- plays a central role in cardiac adaptations towards physiological loading. In conclusion, the maladaptive adaptation towards physiological loading of the heart seems to be dependent on altered Stat3 phosphorylation at Y705 in Parvb-/- hearts.