Clotting kinetic differs between the species, which is not only of clinical interest, but could also be an important finding for animal models of blood coagulation.
Rats impress by their high platelet count resulting in hypercoagulability, which protects the animals from severe bleeding. However, platelets also import numerous stiff junction points into the fibrous system of a clot, also enhancing the pre-stress of the fibrin fibers, which lowers their deformability. Clot deformation is clinically important since large strains are present in the arterial tree (caused by the propagation of pressure and pulse waves), and a clot is considered “safe” when it can deform over a long range of strain amplitudes. We tested clot formation and the behavior of fully formed blood clots of laboratory rats at large sinusoidal shear stress amplitudes by rheometry and compared outcomes to human reference data. We found that fiber density (by scanning electron microscopy) and clot stiffness was pronounced compared to humans and differed with sexual dimorphism and with rat strain. Using our large amplitude oscillation (LAOS) protocol, we detected that rat clots yielded with a frustrated attempt to stiffen instead of showing the macroscopic stiffening response that is typical for human clots. We attribute this behavior to the appearance of multiple microfractures until, finally, a few leading fibers uptake the load. Rat clots also failed to align fibers in shear direction to initiate affine deformation. The rat clot phenotype differs substantially from the human one, which must be considered in research and toxicological testing. If microfractures in the fiber meshwork are concentrated in vivo, parts of a clot may break off and be washed away. However, homogenously distributed microfractures may open pores and allow the penetration of plasminogen activators. What occurs in the rat vasculature depends on the on-site clot composition.
Osteoarthritis (OA) is the most common degenerative joint disease causing pain and functional limitations. Physical activity as a clinically relevant, effective intervention alleviates pain and promotes joint function. In chondrocytes, perception and transmission of mechanical signals are controlled by mechanosensitive ion channels, whose dysfunction in OA chondrocytes is leading to disease progression. Signaling of mechanosensitive ion channels Piezo/TRPV4 was analyzed by Yoda1/GSK1016790A application and calcium-imaging of Fura-2-loaded chondrocytes. Expression analysis was determined by qPCR and immunofluorescence in healthy vs. OA chondrocytes. Chondrocytes were mechanically stimulated using the Flexcell™ technique. Yoda1 and GSK1016790A caused an increase in intracellular calcium [Ca2+]i for Yoda1, depending on extracellularly available Ca2+. When used concomitantly, the agonist applied first inhibited the effect of subsequent agonist application, indicating mutual interference between Piezo/TRPV4. Yoda1 increased the expression of metalloproteinases, bone-morphogenic protein, and interleukins in healthy and OA chondrocytes to a different extent. Flexcell™-induced changes in the expression of MMPs and ILs differed from changes induced by Yoda1. We conclude that Piezo1/TRPV4 communicate with each other, an interference that may be impaired in OA chondrocytes. It is important to consider that mechanical stimulation may have different effects on OA depending on its intensity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.