Effects of diabetes and insulin treatment of diabetic rats on hyaluronan and hyaluronectin production in injured aorta.
The present study was conducted to determine the effect of diabetes with and without insulin treatment on the production of hyaluronen (HA) and distribution of hyaluronectin (HN) in the rat aorta 14 days after injury with a catheter balloon. Injury increased intima-media wet weight (+11%) and DNA content (+37.5%). This increase was slightly enhanced in untreated diabetic rats (+14.7% for wet weight and +48.9% for DNA content) and was significantly greater in diabetic rats treated with insulin (+28.9% for wet weight and +54% for DNA content). HA content increase in the injured aorta of nondiabetic rats (+43.6%) was similar in untreated diabetic (+44.7%) and more pronounced in diabetic rats treated with insulin (+91.3%). HA was markedly expressed in the neointima of nondiabetic rats, particularly near the lumen of the aorta. In untreated diabetic rats, HA was present throughout the neointima and not mainly close to the lumen. HA staining in the neointima of diabetic rats treated with insulin was similar to that in nondiabetic rats. HN was strongly expressed throughout the neointima of all groups. Injury enhanced the production of a high molecular mass HN (>400 kDa); this was not observed either in untreated or in insulin-treated diabetic rats. In conclusion, insulin treatment promoted the proliferative response of aorta to injury and this was associated mainly with increased HA production. This finding suggests that HA, which has been shown to play a crucial role in smooth muscle cell proliferation and migration, may be involved in the promoting effect of insulin treatment on arterial wall reaction to injury.
Chajara
A
A
Laboratoire DIFEMA-MERCI, Faculté de Médecine-Pharmacie, CHU Rouen-Bois-Guillaume, Rouen, France. Abdesslam.Chajara@univ-rouen.fr
Raoudi
M
M
Delpech
B
B
Courel
M
M
Leroy
M
M
Basuyau
J P
JP
Levesque
H
H
D000818:Animals; D001011:Aorta / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000737:chemistry; D004247:DNA / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D006023:Glycoproteins / Q000096:biosynthesis* / Q000737:chemistry; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008970:Molecular Weight; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D012016:Reference Values; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology; D014949:Wounds, Nonpenetrating / Q000378:metabolism*
D002352:Carrier Proteins; D006023:Glycoproteins; D007004:Hypoglycemic Agents; D007328:Insulin; C108676:hyaluronectin protein, human; D006820:Hyaluronic Acid; D004247:DNA