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Abstract: Fibrinogen-like protein 2 (fgl2), a novel prothrombinase, is involved in microthrombosis. We examined fgl2 expression in the glomerular and tubulointerstitial capillaries and its correlation with microthromsis in rats with streptozocin-induced type 2 diabetic nephropathy. Our RT-PCR and immunoblotting analysis showed that fgl2 mRNA and protein levels were increased in microvascular endothelial cells of the glomeruli and renal interstitia at week 19 and became significantly elevated with the development of diabetic nephropathy (P < 0.01). Fgl2 was not or only weakly expressed in the renal tissues of normal rats. Furthermore, a direct significant correlation (r = 0.543, P < 0.01) was found between fgl2 expression and microthrombotic capillaries in the renal tissues. Enzyme linked immunosorbent assays (ELISA) additionally showed that circulating TNF-α levels in rats with type 2 diabetes were significantly elevated and closely correlated with fgl2 expression (r = 0.871, P < 0.01). Our results suggest that fgl2 may activate renal microthrombosis, thus contributing to glomerular hypertension and renal ischemia. [Copyright &y& Elsevier]

Background: Vascular smooth muscle cell (VSMC) proliferation plays an important role in the failure of autologous vein grafts. The c-myc gene activation is highly involved in the VSMC proliferation. In this study, we made an attempt to determine whether VSMC proliferation and vein graft restenosis could be attenuated by silencing the c-myc gene with small interference RNA (siRNA). Methods: The effects of c-myc siRNA on VSMCs in vitro were examined both in cell proliferation and c-myc expression. Thirty-two Sprague-Dawley rats underwent autologous jugular vein to carotid artery reverse interposition grafting and were randomly divided in to four groups. Vein grafts were treated with pluronic gel or gel containing a scrambled siRNA or c-myc siRNA and the control group received no treatment. Intimal thickness of the vein grafts was evaluated at 3 wk after the surgery. Results: In vitro, c-myc siRNA inhibited cell proliferation by 40%, reduced c-myc mRNA level by 70%, and c-myc protein level by 50% compared with the controls. In vivo, the c-myc siRNA treatment reduced intimal hyperplasia by 75%. Conclusions: Our data suggested that c-myc siRNA, when given immediately after the surgery, is an effective approach for the prevention of vein graft restenosis. [Copyright &y& Elsevier]

Abstract: Vascular calcification is a pathobiological process which leads to high morbidity and mortality in cardiovascular disease. The association between vascular calcification and osteoporosis has been reported widely, and there are close relationships among vascular calcification, related cardiovascular disease and osteoporosis, but the biochemical mechanism of vascular calcification is presently unclear. For exploring the possible mechanism of artery calcification we established aorta calcification in an animal model with vitamin D3 and warfarin and tested the effect of alendronate on the expression of osteopontin and osteoprotegerin in calcified aorta tissue of the rat through measuring gene and protein expression of osteopontin and osteoprotegerin respectively. The results indicated compared with control group, the aortic calcium content of calcification group was obviously increased, osteopontin mRNA and osteoprotegerin mRNA were significantly reduced, and osteoprotegerin and osteopontin protein expressions were reduced. Compared with calcification group, the aortic calcium content of alendronate group was obviously reduced, osteopontin mRNA and osteoprotegerin mRNA were significantly increased, and osteopontin and osteoprotegerin protein expression were increased. We conclude that artery calcification may reduce the expression of osteopontin and osteoprotegerin. Alendronate may inhibit rat aorta calcification by up-regulating osteopontin and osteoprotegerin expression. [Copyright &y& Elsevier]