Upregulated and downregulated transcription of myocardial genes after pulmonary artery banding in pigs

Abstract

Background: Acute or chronic pressure overload may occur during or after cardiac surgical procedures. Typical examples are aortic cross-clamping and pulmonary artery banding. It is well known that mechanical stress induces transcription of different myocardial genes. However, these results were mainly obtained from in vitro studies and experiments with rodents. This experiment was carried out to investigate molecular alterations after pressure overload in porcine hearts.

Methods: The study was performed with 35 Landrace pigs with a mean weight of 32+/-1.2 kg. The five groups consisted of 7 pigs each, 3 sham-operated pigs and 4 banded pigs. The hearts were exised after different time intervals. We investigated messenger RNA expression of sarcoplasmic reticulum adenosine triphosphatase, phospholamban, alpha-/beta-myosin heavy chain, and atrial natriuretic factor by Northern blot analysis.

Results: The ratio of right ventricular weight to body weight increased significantly after 7 and 24 days in banded pigs (p < 0.05). Atrial natriuretic factor messenger RNA was significantly upregulated in banded pigs versus sham-operated pigs after 1 day (240%+/-7% versus 100%+/-6%; p < 0.01) and 3 days (520%+/-8% versus 100%+/-8%; p < 0.01). There was insignificant downregulation of sarcoplasmic reticulum adenosine triphosphatase and phospholamban after 1, 3, and 7 days. Myosin heavy chain messenger RNA expression remained unchanged.

Conclusions: Pulmonary artery banding results in hypertrophic response of the porcine right ventricle; however, the weight increase is not the result of myosin heavy chain messenger RNA upregulation. Atrial natriuretic factor messenger RNA is locally expressed in mechanically stressed myocytes. Furthermore, pressure overload downregulates transcription of calcium-binding proteins that can influence ventricular contractility. These results may have an impact on cardiac surgical procedures.