Endothelial cells in culture have, in the past, been a valuable but capricious tool to test hypotheses on the role of components of the blood vessel wall in such functions as blood pressure homeostasis, hemostasis, permeability, transport of macromolecules and the processing of circulating biologically active substances. Now techniques are becoming available for raising long‐term, large‐scale cultures that can be maintained reproducibly and without loss of phenotypic characteristics. The outlook for establishing endothelial cell factories invites speculation on some far‐reaching (...) possibilities, such as endothelial cell banks that could be used for seeding autogenous cells on vascular prostheses, artificial kidney tubing, heart valves, or corneas, or for virus production, or for synthesis by endothelial cells of products at present beyond the reach of bacterial cells. (shrink)

The human blood coagulation system comprises a series of linked glycoproteins that upon activation induce the generation of downstream enzymes ultimately forming fibrin. This process is primarily important to arrest bleeding (hemostasis). Hemostasis is a typical example of a molecular machine, where the assembly of substrates, enzymes, protein cofactors and calcium ions on a phospholipid surface markedly accelerates the rate of coagulation. Excess, pathological, coagulation activity occurs in “thrombosis”, the formation of an intravascular clot, which in the most (...) dramatic form precipitates in the microvasculature as disseminated intravascular coagulation. Thrombosis occurs according to a biochemical machine model in the case of atherothrombosis on a ruptured atherosclerotic plaque, but may develop at a slower rate in venous thrombosis, illustrating that the coagulation machinery can act at different velocities. The separate coagulation enzymes are also important in other biological processes, including inflammation for which the rapid conversion of one coagulation factor by the other is not a prerequisite. The latter role of coagulation enzymes may be related to the old and probably maintained function of the coagulation machine in innate immunity. BioEssays 25:1220–1228, 2003. © 2003 Wiley Perioicals, Inc. (shrink)

In the context of macroevolutionary transitions, environmental changes prompted vertebrates already bearing genetic variations to undergo gradual adaptations resulting in profound anatomical, physiological, and behavioral adaptations. The emergence of new genes led to the genetic variation essential in metazoan evolution, just as was gene loss, both sources of genetic variation resulting in adaptive phenotypic diversity. In this context, F12‐coding protein with defense and hemostatic roles emerged some 425 Mya, and it might have contributed in aquatic vertebrates to the transition from (...) water‐to‐land. Conversely, the F12 loss in marine, air‐breathing mammals like cetaceans has been associated with phenotypic adaptations in some terrestrial mammals in their transition to aquatic lifestyle. More recently, the advent of technological innovations in western lifestyle with blood‐contacting devices and harmful environmental nanoparticles, has unfolded new roles of FXII. Environment operates as either a positive or a relaxed selective pressure on genes, and consequently genes are selected or lost. FXII, an old dog facing environmental novelties can learn new tricks and teach us new therapeutic avenues. (shrink)