The vascular endothelium, a monolayer of endothelial cells (EC), constitutes the inner cellular lining of arteries, veins and capillaries and therefore is in direct contact with the components and cells of blood. The endothelium is not only a mere barrier between blood and tissues but also an endocrine organ. It actively controls the degree of vascular relaxation and constriction, and the extravasation of solutes, fluid, macromolecules and hormones, as well as that of platelets and blood cells. Through control of vascular tone, EC regulate the regional blood flow. They also direct inflammatory cells to foreign materials, areas in need of repair or defense against infections. In addition, EC are important in controlling blood fluidity, platelet adhesion and aggregation, leukocyte activation, adhesion, and transmigration. They also tightly keep the balance between coagulation and fibrinolysis and play a major role in the regulation of immune responses, inflammation and angiogenesis. To fulfill these different tasks, EC are heterogeneous and perform distinctly in the various organs and along the vascular tree. Important morphological, physiological and phenotypic differences between EC in the different parts of the arterial tree as well as between arteries and veins optimally support their specified functions in these vascular areas. This review updates the current knowledge about the morphology and function of endothelial cells, particularly their differences in different localizations around the body paying attention specifically to their different responses to physical, biochemical and environmental stimuli considering the different origins of the EC.

Endothelial cells of the arterial vascular system and the heart contain straight actin filament bundles, of which there are few, if any, in the venous endothelium. Since stress fibre-containing endothelial cells within the vascular system tend to be located at sites exposed to particularly high shear stress of blood flow, we have investigated, in an experimental rheological system (Fig. 1), the response of the endothelial actin filament skeleton to controlled levels of fluid shear stress. Here we report that endothelial stress fibres can be induced by a 3-h exposure of confluent monolayer cultures of human vascular endothelium to a fluid shear stress of 2 dynes cm-2, approximately the stress occurring in human arteries in vivo. Fourfold lower levels of shear stress that normally occur only in veins, had no significant effect on the endothelial actin filament system. The formation of endothelial stress fibres in response to critical levels of fluid shear stress is probably a functionally important mechanism that protects the endothelium from hydrodynamic injury and detachment.

This independence is of practical importance, at least for the medical application of photobiological effects achieved at low-energy density levels, accounting for the success and the failure in most of the cold laser uses since Mester's pioneering work.

A rheological in vitro system has been developed to study and quantify cellular adhesion under precisely defined external shear forces. The system is similar to a cone-and-plate viscosimeter. A rotating transparent cone produces both steady and pulsatile flow profiles on cultured cells. Direct visualization of cells by phase-contrast or fluorescence optics and connection of the optical system to a computer-controlled x/y-linear stage allows automatic recording of any point of the cell cultures. With the use of up to 12 individual rheological units, this setup allows the quantitative analysis of cell substrate adhesion by determination of cell detachment kinetics. Two examples of application of this rheological system have been studied. First, we show that the extracellular matrix protein laminin strongly increases endothelial cell adhesion under fluid shear stress. In a second approach, we obtained further support for the concept that shear stress-induced formation of actin filament stress fibers is important for endothelial cells to resist the fluid shear stress; inhibition of stress fiber formation by doxorubicin resulted in significant detachment of endothelial cells exposed to medium levels of fluid shear stress (5 dyn/cm2). No detachment was seen under resting conditions.

There is growing evidence that COVID-19 not only affects the lungs but beyond that the endothelial system. Recent studies showed that this can lead to microcirculatory impairments and in consequence to functional disorders of all inner organs. The combination of endothelial dysfunction with a generalized inflammatory state and complement elements may together contribute to the overall pro-coagulative state described in COVID-19 patients leading to venular as well as to arteriolar occlusions.

Immediately after viral infection, innate responses including expression of IFN-α/β and IFN-stimulated genes (ISGs) are elicited ubiquitously by recruitment of specific pathogen recognition receptors. The velocity to induce IFN-α/β and ISGs in response to an infection is often decisive for virulence. Interestingly, in primary endothelial cells ISGs are induced later by hantaviruses pathogenic to humans than those considered to be nonpathogenic or of low virulence. Here we demonstrate that pathogenic Hantaan (HTNV) and putatively nonpathogenic Prospect Hill hantavirus (PHV) differentially activate innate responses in the established cell lines A549 and HuH7. STAT1α phosphorylation was detectable 3 h after PHV inoculation but not within the first 2 days after HTNV inoculation. The velocity to induce the ISGs MxA and ISG15 correlated inversely with amounts of virus produced. Moreover, expression of the inflammatory chemokine CCL5 was also induced differentially. Both hantaviruses induced innate responses via TRAF3 (TNF receptor-associated factor 3), and TLR3 was required for HTNV-induced expression of MxA, but not for the MxA induction triggered by PHV. Infection of RIG-I-deficient HuH7.5 cells revealed that RIG-I (retinoic acid receptor I) was not necessary for induction of innate responses by PHV. Taken together, these data suggest that HTNV and PHV elicit different signaling cascades that converge via TRAF3. Early induction of antiviral responses might contribute to efficient elimination of PHV. Subsequent to clearance of the infection, innate responses most likely cease; vice versa, retarded induction of antiviral responses could lead to increased HTNV replication and dissemination, which might cause a prolonged inflammatory response and might contribute to the in vivo virulence.

Experiments designed to mimic cell receptor structures on biomaterial surfaces showed that slow evaporation of water-based suspensions containing polystyrene nanospheres created translucent nanostructured films enclosed by highly regular ring shaped patterns. Our finding represents a novel method to functionalize biomaterial surfaces by structurizing both the micro-and nanoscale topography in one single process, answering practically the complete scale of biological demands required for a better integration of biomaterials into the targeted site of the body.

Recently developed versatile biodegradable polymeric biomaterial offer new therapeutic options in numerous medical fields. Biocompatibility is a crucial requirement for the biomedical application of biomaterials, including the sterilization of these materials with the use of accepted protocols. Ethylene-oxide (EO) and low-temperature plasma (LTP) sterilization are frequently used low-temperature sterilization technologies for heat-sensitive materials. The agarose diffusion assay is a recommended cell-screening test to assess the cytotoxicity of biomaterials in vitro. The sensitivity of the agarose assay can be increased by using a modified computer-based image-analysis system. The influence of EO and LTP sterilization on the cytotoxicity of a versatile polymer system of shape-memory polymer networks based on oligo (epsilon-caprolactone) dimethacrylate and n-butyl acrylate was investigated. Statistically significant differences in the rate of cell lysis after EO and LTP sterilization of the polymer samples were detected by using this modified quantification system. The influence of the different sterilization techniques on the cytotoxicity of the polymeric material, as well as the clinical relevance of the described differences, are discussed.