Accumulation of several basement membrane proteins in glomeruli of patients with preeclampsia and other hypertensive syndromes of pregnancy. Possible role of renal prostaglandins and fibronectin.
The glomerular lesions of preeclampsia consist of swelling of endothelial cells, interposition of mesangial cells and matrix between the endothelial cells and the glomerular basement membrane, and organization of subendothelial deposits of incompletely characterized material. Fibrin and immunoglobulins have previously been localized to these deposits. Laminin, a large basement membrane glycoprotein, type IV collagen, fibronectin, and a basement membrane proteoglycan were found in moderate amounts in the mesangium and prominently in the thickened glomerular capillary walls of patients with preeclampsia or other hypertensive syndromes of pregnancy. Fibrin showed the same pattern of distribution as that of fibronectin. The material deposited in the subendothelial layer of the capillary loops thus consists not only of plasma-derived proteins but also structural components of the glomerular basement membrane and of the mesangial matrix. Type I collagen deposits were demonstrated only in mesangium of pregnant patients with chronic or recurrent hypertension. Glomerular epithelial and mesangial cells synthesize in vitro the basement membrane proteins that accumulate in glomeruli of pregnant hypertensive patients. We have tested the influence of some of the pathophysiologic changes occurring during preeclampsia on the biosynthesis of collagen by rat glomerular epithelial and mesangial cells. Addition of indomethacin to the cultures transiently inhibited the synthesis of prostaglandins (PGE2) and of collagen. Addition of exogenous fibronectin to the media stimulated the production of collagen by mesangial and epithelial cells. Alterations in the metabolism of prostaglandins and the increased deposition of fibronectin observed during preeclampsia could thus play a pathogenic role in the accumulation of basement membrane proteins in glomeruli of these patients.
D001485:Basement Membrane / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D007797:Laminin; D008565:Membrane Proteins / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism
D005353:Fibronectins; D006023:Glycoproteins; D007797:Laminin; D008565:Membrane Proteins; D011453:Prostaglandins; D005337:Fibrin; D003094:Collagen; D007213:Indomethacin