Angiotensin converting enzyme inhibition reduces the expression of transforming growth factor-beta1 and type IV collagen in diabetic vasculopathy.
OBJECTIVE
The purpose of this study was to assess the role of transforming growth factor (TGF)-beta1 in the development of diabetes-associated mesenteric vascular hypertrophy and in the antitrophic effect of angiotensin converting enzyme inhibitors.


METHODS
Streptozotocin-induced diabetic and control Sprague-Dawley rats were randomly allocated to treatment with the angiotensin converting enzyme inhibitor ramipril or to no treatment and were killed 1 or 3 weeks after the streptozotocin injection. Blood was collected and mesenteric vessels removed. Mesenteric vascular weight was measured and TGF-beta1 and alpha1 (type IV) collagen messenger (m)RNA levels were analysed by Northern analysis. Immunohistochemical analyses for TGF-beta1 and type IV collagen were also performed.


RESULTS
The diabetic rats had increased mesenteric vessel weight at 3 weeks but not at 1 week and a concomitant rise in mesenteric TGF-beta1 and in alpha1 (type IV) collagen mRNA levels. Ramipril treatment attenuated mesenteric vessel hypertrophy and prevented the increase in TGF-beta1 and alpha1 (type IV) collagen mRNA levels after 3 weeks of diabetes. The immunohistochemical analysis revealed that diabetes was associated with increased TGF-beta1 and type IV collagen protein and extracellular matrix accumulation in mesenteric vessels, and this increase was reduced by ramipril treatment.


CONCLUSIONS
These results support the concept that TGF-beta is involved in the changes associated with diabetic vascular disease, and suggest a mechanism by which angiotensin converting enzyme inhibitors exert their antitrophic effects.
Rumble
J R
JR
Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg, Australia.
Gilbert
R E
RE
Cox
A
A
Wu
L
L
Cooper
M E
ME
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D015152:Blotting, Northern; D001835:Body Weight / Q000187:drug effects; D003094:Collagen / Q000235:genetics*; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003925:Diabetic Angiopathies / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014652:Vascular Diseases / Q000150:complications / Q000235:genetics / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen; D017257:Ramipril