Question:

Cardiac hypertrophy depends on focal adhesions, which are recruited to integrin cytoplasmic domains. A protein assembly of Ilk, Pinch and the F-actin binding protein parvin (IPP) is critical for myocard integrity as further is an adequate capillarization of the myocard. Disturbed capillary adaptations towards physiological loading result in maladaptive cardiac phenotypes. Stat3 is a potent regulator of capillarization and is regulated by Parvb, why we hypothesized that Parvb deletion (Parvb-/-) leads to pathological cardiac adaptations.

Methodology:

Mouse echocardiography was performed in transverse aortic constriction (TAC) and chronically trained WT and Parvb-/- mice. Chronic treadmill exercise was performed over 4 wks (5x/wk, 18m*min-1, angle 10°). Acute treadmill exercise consisted of a single 15min exercise bout. Capillarization was investigated histologically. Total Stat3/Stat3Tyr705 was quantified by WB in control, chronic/acute exercised and TAC hearts.

Results:

We did not observe any cardiac phenotype in Parvb-/- under resting conditions. Chronic exercise resulted in decreased capillarization in Parvb-/- cardiomyocytes. We observed that acute exercise led to decreased Stat3Y705 phosphorylation in Parvb-/- hearts compared to WT. Capillarization was higher in WT-TAC and Parvb-/--TAC conditions compared to controls. However, we did not find differences in capillarization between WT-TAC and Parvb-/--TAC. Stat3Y705 did not significantly differ between WT-TAC and Parvb-/--TAC hearts, but was higher compared to control conditions.

Conclusion:

Our 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.