Heparin inhibits mesangial cell proliferation in habu-venom-induced glomerular injury.
The authors have investigated the ability of anticoagulant heparin and nonanticoagulant heparin to inhibit mesangial-cell proliferation after the administration of habu (Trimeresurus flavorivids) snake venom to rats. Rats given injected habu venom exhibited glomerular capillary cystic lesions 6 to 24 hours later, and marked mesangial proliferation was noted within the cyst after 3 days. At 7 days 87% of these lesions (nodules) contained primarily mesangial cells embedded in a dense matrix and fibrin. A decrease in the frequency of nodules and the persistence of cysts indicate effective antiproliferative treatment. When anticoagulant heparin treatment extended from 18 hours after venom administration until sacrifice at 7 days, the percentage of nodules was reduced to 40%. Nonanticoagulant heparins resulted in some, but inconsistent, inhibition of mesangial-cell proliferation. The mechanism of the antiproliferative action of heparin on mesangial cells is not known but may be similar to that for vascular smooth muscle growth regulation. The authors suggest that endogenous heparin in the glomerular basement membrane and mesangial matrix may exert an antiproliferative effect under normal conditions. Loss of this inhibition due to glomerular damage might be reversed by the addition of exogenous heparin.
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001485:Basement Membrane / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003435:Crotalid Venoms / Q000633:toxicity*; D004727:Endothelium / Q000378:metabolism; D005260:Female; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006493:Heparin / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew
D000925:Anticoagulants; D003435:Crotalid Venoms; D006493:Heparin