Tranilast reduces mesenteric vascular collagen deposition and chymase-positive mast cells in experimental diabetes.
The mast cell has a central role in the pathogenesis of fibrosis a common feature of diabetic microvascular complications. Increased mast cell numbers have been demonstrated in diabetic nephropathy in association with renal fibrosis, and diabetes acutely increases mast cell infiltration in the mesentery. Antimast cell agents such as tranilast may ameliorate the acute vascular changes in diabetes due to stabilisation of mast cells and/or reduction in mast cell numbers. After 3 weeks of streptozotocin diabetes, light microscopy techniques were used to estimate mesenteric vessel fibrosis and mast cell infiltration. Mast cells were identified by toluidine blue staining and tryptase, chymase and TGF-beta immunohistochemistry in three study groups of rats: control, diabetic and plus tranilast. Diabetes was associated with an increase in both mesenteric vessel fibrosis and mast cell numbers. Administration of tranilast to diabetic rats reduced mesenteric vessel fibrosis and this was associated with a reduction in chymase-positive mast cells. These changes were independent of mast cell TGF-beta and were not associated with a reduction in tryptase-positive mast cells. The amelioration of diabetes-induced vessel fibrosis may be due to a reduction in the liberation of angiotensin II by inhibiting mast cell chymase.
Jones
S E
SE
Department of Medicine, University Hospital of Hartlepool, Hartlepool, UK.
Gilbert
R E
RE
Kelly
D J
DJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002452:Cell Count; D053818:Chymases; D003094:Collagen / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D005355:Fibrosis; D007150:Immunohistochemistry; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008638:Mesenteric Arteries / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D062367:ortho-Aminobenzoates; D003094:Collagen; D012697:Serine Endopeptidases; D053818:Chymases; C012293:tranilast