GENE-EXPRESSION IN A SWINE MODEL OF RIGHT-VENTRICULAR HYPERTROPHY - INTERCELLULAR-ADHESION MOLECULE, VASCULAR ENDOTHELIAL GROWTH-FACTOR ANDPLASMINOGEN 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 p ulmonary artery so that right ventricular pressure was increased two-f old. The heart was harvested at 3, 7, 24 and 72 h after surgery. Betwe en 7 and 72 h there was evidence of muscle damage and inflammation, No rthern blot experiments showed that pressure overload induced a transi ent increase in the expression of the immediate early genes and in the developmentally regulated atrial natriuretic factor and skeletal musc le alpha actin genes, Consistent with the histological observations of inflammation, increases in the expression of the gene for intercellul ar 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 cel ls was increased at 3 and 7 h of pressure overload. An increase in the expression of urokinase plasminogen activator and its inhibitors, pla sminogen activator inhibitors I and II, was also observed between 3 an d 24 h. This was associated with an increase in urokinase activity in the myocardial tissue, These results indicate that hypertrophy in a la rge mammal such as swine induces a program of gene expression similar to that previously described in rodents and suggests that up-regulatio n of a variety of other genes is an early response to pressure overloa d. (C) 1995 Academic Press Limited