Background: Dysfunctions of the cardiac mitral and aortic valves create a continuous hemodynamic stress on the left ventricle (LV), leading to its progressive remodeling, hypertrophy and eventually congestive heart failure. Periostin, a secreted extracellular protein, was recently reported to be involved in regulating cardiac hypertrophy and interstitial fibrosis due to pressure overload stimulation and myocardial infarction. However its role in volume overload- induced heart failure is still unknown.
Working hypothesis: We hypothesize that elevated expression of Periostin in the heart under chronic mechanical stress may correlate with the severity of LV dilatation.
Methods and results: We established a rat model for volume overload by introducing aorto-caval shunt (fistula) between exposed abdominal aorta and vena cava. Rats subjected to aortocaval fistula (ACF) showed an increase in heart-to body weight ratio compared to control animals as early as two weeks after shunt introduction (4.3±0.0002 mg versus 3.4±0.005 mg, respectably). Twenty weeks after fistula formation, heart-to body weight ratio continued to increase (6.7±0.002 mg versus 3.4±0.0002 in sham). Echocardiographic imaging studies demonstrated an elevation of LV end-diastolic volume in ACF animals four weeks after fistula formation, compared to sham-operated controls (0.535±0.035 cm vs. 0.37±0.01 cm). Sixteen weeks later, LV dilatation continued to progress (0.756±0.032 cm versus. 0.49±0.015). Concomitantly, an increase in mRNA expression of Postn (Periostin coding gene) was detected by real-time PCR twenty weeks after ACF creation both in LV sections (90-fold) and in isolated cardiac fibroblasts (32-fold).
Conclusion: Periostin as a substrate of a variety of integrins, may affect signaling within cardiac myocytes and fibroblasts. We believe that alterations in integrins engagement may eventually culminate in the observed dilatation by side to side slippage of cardiomyocytes. Periostin, may thus represent a novel therapeutic target for attenuating cardiac deterioration into heart failure in patients suffering from chronic volume overload.
