GENE-EXPRESSION IN A SWINE MODEL OF RIGHT-VENTRICULAR HYPERTROPHY - INTERCELLULAR-ADHESION MOLECULE, VASCULAR ENDOTHELIAL GROWTH-FACTOR AND PLASMINOGEN ACTIVATORS ARE UP-REGULATED DURING PRESSURE-OVERLOAD

We have investigated the molecular changes which occur during pressure overload hypertrophy of the RV in swine. Animals were banded on the pulmonary artery so that right ventricular pressure was increased two-fold. The heart was harvested at 3, 7, 24 and 72 h after surgery. Between 7 and 72 h there was evidence of muscle damage and inflammation, Northern blot experiments showed that pressure overload induced a transient increase in the expression of the immediate early genes and in the developmentally regulated atrial natriuretic factor and skeletal muscle alpha actin genes, Consistent with the histological observations of inflammation, increases in the expression of the gene for intercellular adhesion molecule, which encodes a protein involved in the binding of leukocytes by endothelial cells and myocytes, was observed between 3 and 24 h. In addition, the expression of vascular endothelial growth factor, a growth and permeability factor specific for endothelial cells was increased at 3 and 7 h of pressure overload. An increase in the expression of urokinase plasminogen activator and its inhibitors, plasminogen activator inhibitors I and II, was also observed between 3 and 24 h. This was associated with an increase in urokinase activity in the myocardial tissue, These results indicate that hypertrophy in a large mammal such as swine induces a program of gene expression similar to that previously described in rodents and suggests that up-regulation of a variety of other genes is an early response to pressure overload. (C) 1995 Academic Press Limited