[Effects of angiotensin II and pressure on cellular fibronectin in the vascular wall in organotypic culture].
Fibronectin is a dimeric glycoprotein found in the extracellular matrix of most tissues, which can influence processes, including cell growth, adhesion and migration. Fibronectin synthesis has been shown to be overexpressed in hypertension. However, the respective effects of humoral factors, including angiotensin II, versus mechanical factors in vascular remodeling have not yet been clarified. To study fibronectin de novo synthesis in the arterial wall, we have developed a new model for organ culture of rabbit thoracic aorta. Arteries held at their in vivo length were incubated and perfused (40 ml/min) in DME medium containing 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 incubator at 37 degrees C under 5% CO2. De novo synthesis of fibronectin was detected by immunofluorescence using anti-cellular fibronectin antibodies (1/200). In the absence of angiotensin II and serum, fibronectin was expressed in the sub-endothelium at 80 mmHg, and in the inner media at 150 mmHg. In the presence of serum, fibronectin expression was increased by the high pressure. When angiotensin II was added, a gradient of fibronectin became apparent in the inner media at 80 mmHg with a marked expression at the luminal side. Angiotensin II markedly enhanced fibronectin expression at 150 mmHg, the protein being detected in almost the whole media. Our results indicate that both angiotensin II and transmural pressure can induce fibronectin expression in the arterial wall, and both act synergically.
Bardy
N
N
INSERM U141, hôpital Lariboisière, Paris.
Merval
R
R
Samuel
J L
JL
Tedgui
A
A
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D005353:Fibronectins / Q000096:biosynthesis / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism; D008297:Male; D011817:Rabbits
D005353:Fibronectins; D000804:Angiotensin II
Effets de l'angiotensine II et de la pression sur l'expression de la fibronectine cellulaire dans la paroi vasculaire en culture organotypique.