Cellular mechanisms of diabetic vascular hypertrophy

Mesenteric vascular hypertrophy occurs in experimental diabetes. The present study examines whether this medial hypertrophy originates via cellular hyperplasia or hypertrophy of smooth muscle cells or an increase in collagen content. Male Sprague-Dawley diabetic (streptozotocin, 50 mg/kg, i.v.) rats were compared with control rats after 3 weeks in order to study mesenteric and aortic smooth muscle cell size and degree of cellular polyploidy. Collagen content in the mesenteric vessels was examined via staining with Sirius red. Further groups of control and diabetic animals were studied after 7 and 14 days of diabetes to assess proliferation in the various layers of the vessel wall using incorporation of [3H]thymidine (0.5 mCi/kg, i.p.). Smooth muscle cell size was measured by a Coulter counter and polyploidy assessed using flow cytometry measurement of cellular DNA content. Diabetic smooth muscle cell size was reduced in both the aorta and the mesenteric vessels and polyploidy was increased in these cells. The collagen content of diabetic mesenteric media was proportionally increased. At day 7, diabetic mesenteric endothelial and adventitial layers showed increased [3H]thymidine labeling of cells and this was not observed in the media of these vessels. These findings indicate that increased endothelial and adventitial cell proliferation are early events in diabetes associated vascular hypertrophy. Furthermore, an increase in extracellular matrix within the media is an important feature of diabetes associated vascular hypertrophy.