Lipid-mediated inflammation and degeneration of bioprosthetic heart valves.

BACKGROUND: The durability of bioprosthetic valves is limited by structural valve degeneration (SVD) leading to bioprostheses (BPs) stenosis or regurgitation. We hypothesized that a lipid-mediated inflammatory mechanism is involved in the SVD of BPs. MATERIAL AND METHODS: Eighteen Freestyle stentless BP valves were explanted for SVD at a mean time of 5.9 +/- 3 years after implantation and were analysed by immunohistochemistry and transmission electron microscopy (TEM). RESULTS: The mean age of the patients was 65 +/- 8 years and there were 11 male and seven female patients. Two of the 18 BPs had macroscopic calcification, whereas the other valves had minimal or no macroscopic calcification. Tears at the commissures leading to regurgitation was present in 16 BPs. Immunohistochemistry showed the presence of oxidized low-density lipoprotein (ox-LDL) and glycosaminoglycans in the fibrosa layer of 13 BPs. Areas with ox-LDL were infiltrated by macrophages (CD68(+)) co-expressing the scavenger receptor CD36 and metalloproteinase-9 (MMP-9). Zymogram showed the active form of MMP-9 within explanted BPs. EM studies revealed the presence of lipid-laden cells featuring foam cells and fragmented collagen. Nonimplanted control BPs obtained from the manufacturer (n = 4) had no evidence of lipid accumulation, inflammatory cell infiltration or expression of MMP9 within the leaflets. CONCLUSIONS: These results support the concept that lipid-mediated inflammatory mechanisms may contribute to the SVD of BPs. These findings suggest that modification of atherosclerotic risk factors with the use of behavioural or pharmacological interventions could help to reduce the incidence of SVD.

Stromal fibroblasts are required for PC-3 human prostate cancer cells to produce capillary-like formation of endothelial cells in a three-dimensional co-culture system.

The outcome of patients with prostate cancer is largely dependent on the ability of the primary tumor for local invasion, angiogenesis and metastasis. To better understand the cell-cell interactions that participate in prostate cancer neovascularization, we have developed a novel three-dimensional co-culture system. Capillary-like structures were induced in fibrin gel in which collagen gels containing fibroblasts and/or PC-3 human prostate adenocarcinoma cells were sandwiched together. In the presence of collagen-embedded fibroblasts, angiogenesis apparently occurred, while endothelial cells did not survive when only PC-3 cells were embedded in collagen. In contrast, when PC-3 cells were combined with fibroblasts in collagen gel an enhanced formation of capillary-like structure formation was noted, particularly using FGF-2-supplemented medium. In addition, we observed morphological evidence of PC-3 cells and fibroblast invasion into fibrin using this system. Therefore, we conclude that fibroblasts apparently play an important role in angiogenesis and tumor invasion. Furthermore, this novel three-dimensional co-culture is apparently a promising model for studying de novo angiogenesis and tumor invasion in vitro.