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There is accumulating evidence that Alzheimer's disease (AD) can have vascular contribution. In particular, endothelial dysfunction may impair nitric oxide (NO) production and cause cerebral hypoperfusion. Blood flow impairment can be provoked also by an increased production of reactive oxygen species (ROS). The present study was performed in order to investigate the effect of plasma from subjects affected by AD and mild cognitive impairment (MCI) on human aortic endothelial cells (HAECs) in vitro, since endothelial dysfunction has been suggested to be an early event in patients affected by AD. Plasma samples were obtained from 27 AD patients, 15 MCI subjects, and 19 age-and sex-matched healthy subjects. After a short incubation period the following parameters were evaluated: NO release, superoxide dismutase (SOD) and Na+/K+-ATPase activities, membrane fluidity, and thiobarbituric acid-reactive substance (TBARS) production. Exposure to MCI plasma provoked a decrease in NO release, more pronounced in the presence of AD plasma. Our data on SOD and Na+/K+-ATPase activities showed a similar trend, since the lowest values were recorded after incubation with AD plasma. Endothelial membrane fluidity was deeply affected by the exposure to MCI plasma, and even more following incubation with AD plasma. Finally, enhanced TBARS production after incubation with MCI and AD plasma was observed. In conclusion, our results showed that MCI and AD plasma affects endothelial cells, thus highlighting the need for early treatment aimed at protecting the endothelium. [ABSTRACT FROM AUTHOR]

Tissue engineered scaffolds must have an organized and repeatable microstructure which enables cells to assemble in an ordered matrix that allows adequate nutriental perfusion. In this work, to evaluate the reciprocal cell interactions of endothelial and osteoblast-like cells, human osteoblast-like cells (MG63) and Human Umbilical Vein Endothelial Cells (HUVEC) were co-seeded onto 3D geometrically controlled porous poly(ε-caprolactone) (PCL) and cultured by means of a rotary cell culture system (RCCS-4DQ). In our dynamic co-culture system, the lack of significant enhancement of osteoblast ALP activity and ECM production indicated that the microgravity conditions of the rotary system affected the cells by favoring their proliferation and cellular cross-talk. These results emphasize how osteoblasts increase endothelial cell proliferate and endothelial cells amplify the growth of osteoblasts but decrease their differentiation. This dynamic seeding of osteoblasts and endothelial cells onto a 3D polymeric scaffold may represent a unique approach for studying the mechanisms of interaction of endothelial and osteoblast cells as well as achieve a functional hybrid in which angiogenesis, furnished by neo-vascular organization of endothelial cells may further support osteoblasts growth. Furthermore, this in vitro model may be useful in examining the applicability of novel material structures for tissue engineering. [ABSTRACT FROM AUTHOR]