Elevated serum osteoprotegerin is associated with decreased osteoclastic differentiation in stenotic aortic valves.

Calcific aortic valve stenosis (CAVS) is an actively regulated process that involves mechanisms of bone development, including the receptor activator of nuclear factor κB, its ligand, and osteoprotegerin (RANK/RANKL/OPG) regulatory system. The aim of this study was to investigate whether the levels of circulating OPG and RANKL can be correlated with some histopathological features of the stenotic valves. Serum levels of osteoprotegerin (OPG) and soluble RANKL (sRANKL) were assessed in 27 patients with CAVS prior to valve replacement surgery and in 12 control subjects. The removed valves were examined macroscopically and microscopically. Valve sections were stained with hematoxylin and eosin for general morphology, with Oil Red O for lipids and immunostained with antibodies against markers visualizing osteoclastic cells (tartrate-resistant acid phosphatase, TRAP), macrophages (CD68) and blood vessels (CD34). Patients with CAVS had elevated levels of OPG as compared to the control group (p=0.005). Within the CAVS group, patients with osteoclastic TRAP-positive cells in their valves had significantly lower serum levels of OPG (p=0.009) and lipid content (p=0.03) than those without such cells. Moreover, osteogenic metaplasia was observed exclusively in the valves containing TRAP-positive cells. Results of this study suggest that the circulating OPG can influence the processes occurring in the calcifying valves by inhibiting osteoclastic differentiation of cells involved in calcification and by preventing osteogenic metaplasia.

Effect of nebivolol treatment on atherosclerotic plaque components in apoE-knockout mice.

Nebivolol, a third generation beta1-blocker was previously found to reduce the size of atherosclerotic lesions. The aim of this study was to assess the effect of orally administered nevibolol on the components of the atherosclerotic plaque in apoE-deficient mice. The quantitative evaluation of cross-sectioned plaques stained by histological and immunohistochemical techniques revealed that treatment with nebivolol (2.0 µol per kg b.w.) for 4 months caused a decrease in the necrotic core area (by 46%, p=0.03), density of CD68+ macrophages (by 41%, p=0.008) and CD3+ lymphocytes (by 16%, p=0.03), collagen content (by 49%, p=0.008) and the activity area of metalloproteinases (by 48%, p=0.008), as well as an increase in the smooth muscle content of the fibromuscular cap (by 46%, p=0.008). These effects suggest that nebivolol suppresses the inflammatory/immune processes in the plaque and enhances its stability.

Effect of cultured autologous oral keratinocyte suspension in fibrin glue on oral wound healing in rabbits.

The effect of cultured autologous oral keratinocyte suspension in fibrin glue on the healing of surgically produced oral mucosal wounds was assessed in the rabbit model. Using the light microscope and a digital image analysis system, the epithelization parameters (marginal epithelization and percentage of wound re-epithelization) were measured in haematoxylin-eosin stained sections of the wound area and compared with those of wounds treated with fibrin glue alone and untreated ones. The epithelization was significantly higher in keratinocytes plus fibrin glue-treated wounds on postoperative days 3 and 7. No significant differences were observed on postoperative day 1, when the healing process had just begun, and on postoperative day 14, when re-epithelization was completed or nearly completed in all groups. The inflammatory infiltration of the wounded mucosa was weakest in keratinocyte-treated wounds and strongest in untreated wounds. In conclusion, suspension of cultured autologous oral keratinocytes in fibrin glue significantly accelerates oral wound healing in the rabbit model and could be beneficial in the treatment of oral wounds in patients.