Spontaneous diabetes in BB Wistar rats causes small increases in the early proliferative response of smooth muscle cells in re-injured aortae.

Diabetic patients are at greater risk for restenosis following angioplasty, but the mechanisms involved remain unclear. Early proliferative changes in vessels following angioplasty contribute to the subsequent intimal thickening associated with restenosis. Materials released from platelets which interact with the injured vessels and thrombin generated on the injured vessels could be contributory factors. Clinical restenosis occurs following injury to atherosclerotic vessels and, therefore, more relevant animal models of this clinical problem are those involving injury to already diseased vessels. In the present study the effect of spontaneous diabetes in BB Wistar rats was examined on early smooth muscle cell proliferation, as detected by an antibody to PCNA, in the media and intima after re-injury with a balloon catheter to the aorta similarly injured 3 weeks earlier. In studies in which aortae were re-injured 2 weeks after the first injury 51Cr-labeled platelet accumulation was determined and the vessels were examined morphologically for evidence of fibrin, platelet aggregate, or thrombus formation. The number of PCNA-positive cells (P < 0.01) and the percentage of total cells (P < 0.01) in the aortic media of diabetic rats were greater 1 day after re-injury compared to the 2-hr value; after 3 or 7 days this increase had returned to the 2-hr value. No increase occurred in the control rats. The mean percentage of PCNA-positive cells in the aortic intima in diabetic rats was greater 1 (P < 0.025), 3 (P < 0.05), or 7 (P < 0.01) days after re-injury, compared with the 2-hr value. In contrast, a nonsignificant increase occurred later in control rats. Morphological examination of the aortic surface in control and diabetic rats 30 min after re-injury showed only a monolayer of platelets with no evidence of fibrin or thrombus formation. 51Cr-Labeled platelet accumulation and turnover on the re-injured aortic surface were similar in the control and diabetic rats. Therefore, spontaneous diabetes in rats is associated with small increases in the early proliferative response of smooth muscle cells in the aorta to balloon catheter-induced re-injury, which did not result from increased platelet accumulation or thrombosis on the vessel surface. This altered response of vessels to re-injury due to the diabetic state in rats could be a contributory factor to the greater risk for restenosis seen in diabetic patients following clinical angioplasty.