EFFECTS OF ANGIOTENSIN-II AND PRESSURE ON FIBRONECTIN EXPRESSION IN ANEW MODEL OF ORGAN-CULTURE OF RABBIT AORTA

Fibronectin is a dimeric glycoprotein found in the extracellular matri x of most tissues, which can influence processess, including cell grow th, adhesion and migration. Fibronectin synthesis has been shown to be overexpressed in hypertension. However, the respective effects of hum oral factors, including angiotensin II, versus mechanical factors in v ascular remodeling have not yet been clarified. To study fibronectin d e novo synthesis in the arterial wall, we have developed a new model f or organ culture of rabbit thoracic aorta. Arteries held at their in v ivo lenght were incubated and perfused (40 ml/min) in DME medium conta ining antibiotics, supplemented with 20 % fetal calf serum or with 5 % bovine serum albumin. In a series of experiments, angiotensin II (10( -6)M) and indomethacin (10(-5) M) were added to culture media. Vessels were pressurized at 0, 80 or 150 mmHg, and kept for 3 days in incubat or at 37-degrees-C under 5 % CO2. De novo synthesis of firbonectin was detected by immonofluorescence using anti-cellular fibronectin antibo dies (1/200). In the absence of angiotensin II and serum, fibronectin was expressed in the sub-endothelium at 80 mmHg, and in the inner medi a at 150 mmHg. In the presence of serum, fibronectin expression was in creased by the high pressure. When angiotensin II was added, a gradien t of fibronectin became apparent in the inner media at 80 mmHg with a marked expression at the luminal side. Angiotensin II markedly enhance d fibronectin expression at 150 mmHg, the protein being detected in al most the whole media. Our results indicate that both angiotensin II an d transmural pressure can induce fibronectin expression in the arteria l wall, and both act synergically.