Shear stress switches the association of endothelial enhancers from ETV/ETS to KLF transcription factor binding sites.

Endothelial cells (ECs) lining blood vessels are exposed to mechanical forces, such as shear stress. These forces control many aspects of EC biology, including vascular tone, cell migration and proliferation. Despite a good understanding of the genes responding to shear stress, our insight into the transcriptional regulation of these genes is much more limited.

"Fun slipping into the doctor's role"-The relationship between sonoanatomy teaching and professional identity formation before and during the Covid-19 pandemic.

The various psychological dimensions of professional identity formation (PIF) are an important aspect of the study course for undergraduate medical students. Anatomical learning environments have been repeatedly shown to play a critical role in forming such an identity; however, relevance of PIF during sonoanatomical training remains underexplored. At the end of their basic anatomy studies, third-semester medical students took part in a four-day block course on anatomy and imaging.

JAM-A interacts with α3β1 integrin and tetraspanins CD151 and CD9 to regulate collective cell migration of polarized epithelial cells.

Junctional adhesion molecule (JAM)-A is a cell adhesion receptor localized at epithelial cell-cell contacts with enrichment at the tight junctions. Its role during cell-cell contact formation and epithelial barrier formation has intensively been studied. In contrast, its role during collective cell migration is largely unexplored.

Autoregulatory "Multitasking" at Endothelial Cell Junctions by Junction-Associated Intermittent Lamellipodia Controls Barrier Properties.

Vascular endothelial cell (EC) junctions are key structures controlling tissue homeostasis in physiology. In the last three decades, excellent studies have addressed many aspects of this complex and highly dynamic regulation, including cell signaling, remodeling processes of the proteins of tight junctions, adherens junctions, and gap junctions, the cytoskeleton, and post-transcriptional modifications, transcriptional activation, and gene silencing. In this dynamic process, vascular endothelial cadherin (VE-cadherin) provides the core structure of EC junctions mediating the physical adhesion of cells as well as the control of barrier function and monolayer integrity via remodeling processes, regulation of protein expression and post-translational modifications.

EPLIN-α and -β Isoforms Modulate Endothelial Cell Dynamics through a Spatiotemporally Differentiated Interaction with Actin.

Actin-binding proteins are essential for linear and branched actin filament dynamics that control shape change, cell migration, and cell junction remodeling in vascular endothelium (endothelial cells [ECs]). The epithelial protein lost in neoplasm (EPLIN) is an actin-binding protein, expressed as EPLIN-α and EPLIN-β by alternative promoters; however, the isoform-specific functions are not yet understood. Aortic compared to cava vein ECs and shear stress-exposed cultured ECs express increased EPLIN-β levels that stabilize stress fibers.

Holding donated human bodies in conservation: A novel interactive safe-keeping system meeting high ethical and safety standards.

"Mortui vivos docent". Learning from donated bodies is widely considered a corner stone in pre-clinical education, advanced clinical training, and scientific progress in medicine. Making such use of dead human bodies must, of course, accord with high ethical standards and legal constraints.

Putting VE-cadherin into JAIL for junction remodeling.

Junction dynamics of endothelial cells are based on the integration of signal transduction, cytoskeletal remodeling and contraction, which are necessary for the formation and maintenance of monolayer integrity, but also enable repair and regeneration. The VE-cadherin-catenin complex forms the molecular basis of the adherence junctions and cooperates closely with actin filaments. Several groups have recently described small actin-driven protrusions at the cell junctions that are controlled by the Arp2/3 complex, contributing to cell junction regulation.

Advanced Methods for the Investigation of Cell Contact Dynamics in Endothelial Cells Using Florescence-Based Live Cell Imaging.

Endothelial cells of the vascular system are dynamic cells whose molecular adaptability is decisive for the adjustment of homeostasis and organ perfusion. Advanced microscopic techniques, automation processing, and image analysis software was shown to improve the understanding of vascular biology. In this work, we describe advanced methods that allow investigating the dynamics of endothelial cell contacts.

Polarized actin and VE-cadherin dynamics regulate junctional remodelling and cell migration during sprouting angiogenesis.

VEGFR-2/Notch signalling regulates angiogenesis in part by driving the remodelling of endothelial cell junctions and by inducing cell migration. Here, we show that VEGF-induced polarized cell elongation increases cell perimeter and decreases the relative VE-cadherin concentration at junctions, triggering polarized formation of actin-driven junction-associated intermittent lamellipodia (JAIL) under control of the WASP/WAVE/ARP2/3 complex. JAIL allow formation of new VE-cadherin adhesion sites that are critical for cell migration and monolayer integrity.

From basic mechanisms to clinical applications in heart protection, new players in cardiovascular diseases and cardiac theranostics: meeting report from the third international symposium on "New frontiers in cardiovascular research".

In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients' cohorts, the influence of co-morbidities and medications, as well as the contribution of innate immune reactions in cardioprotection. Moreover, developmental or systems biology approaches bear great potential in systematically uncovering unexpected components involved in ischemia-reperfusion injury or heart regeneration. Based on the characterization of particular platelet integrins, mitochondrial redox-linked proteins, or lipid-diol compounds in cardiovascular diseases, their targeting by newly developed theranostics and technologies opens new avenues for diagnosis and therapy of myocardial infarction to improve the patients' outcome.

Contraction of endothelial cells: 40 years of research, but the debate still lives.

Force generation in non-muscle cells is vital for many cellular and tissue functions. Force-generating mechanisms include actomyosin-mediated contraction, actin polymerization that drives plasma membrane protrusions and filopodia as well as kinesin- and dynein-controlled transport of vesicles and organelles along the microtubule cytoskeleton. The actomyosin-mediated contractility and actin remodeling in both epithelium and endothelium were shown to have significant impact on cell migration, shape change and formation and control of intercellular junctions.

Targeting of NADPH oxidase in vitro and in vivo suppresses fibroblast activation and experimental skin fibrosis.

Although there is increasing evidence that oxidative stress is involved in collagen synthesis and myofibroblast activation, the NADPH oxidase (Nox) system is incompletely investigated in the context of human dermal fibroblasts (HDFs) and skin fibrosis. Using the pan-Nox inhibitor diphenyleneiodonium (DPI) as an initial tool, we show that gene expression of collagen type I, α-smooth muscle actin (α-SMA) and fibronectin 1 is suppressed in HDFs. Detailed expression analysis of all Nox isoforms and adaptors revealed expression of RNA and protein expression of Nox4, p22 and Poldip2 but neither Nox1 nor Nox2.

Quantitative dynamics of VE-cadherin at endothelial cell junctions at a glance: basic requirements and current concepts.

Intercellular junctions of the vascular endothelium are dynamic structures that display a high degree of plasticity, which is required to contribute to their regulation of many physiological and pathological processes including monolayer integrity, barrier function, wound healing and angiogenesis. Vascular endothelial cadherin (VE-cadherin) is connected via catenins to the actin cytoskeleton, both of which are key structures in endothelial junction regulation, and thus are the focus of much investigation. Fluorescence-based live cell imaging is the method of choice to study dynamic remodeling in living cells.

Meeting report from the 2nd International Symposium on New Frontiers in Cardiovascular Research. Protecting the cardiovascular system from ischemia: between bench and bedside.

Recent advances in basic cardiovascular research as well as their translation into the clinical situation were the focus at the last "New Frontiers in Cardiovascular Research meeting". Major topics included the characterization of new targets and procedures in cardioprotection, deciphering new players and inflammatory mechanisms in ischemic heart disease as well as uncovering microRNAs and other biomarkers as versatile and possibly causal factors in cardiovascular pathogenesis. Although a number of pathological situations such as ischemia-reperfusion injury or atherosclerosis can be simulated and manipulated in diverse animal models, also to challenge new drugs for intervention, patient studies are the ultimate litmus test to obtain unequivocal information about the validity of biomedical concepts and their application in the clinics.

Actin filament dynamics and endothelial cell junctions: the Ying and Yang between stabilization and motion.

The vascular endothelium is a cellular interface between the blood and the interstitial space of tissue, which controls the exchange of fluid, solutes and cells by both transcellular and paracellular means. To accomplish the demands on barrier function, the regulation of the endothelium requires quick and adaptive mechanisms. This is, among others, accomplished by actin dynamics that interdependently interact with both the VE-cadherin/catenin complex, the main components of the adherens type junctions in endothelium and the membrane cytoskeleton.

Imbalance of SMC1 and SMC3 cohesins causes specific and distinct effects.

SMC1 and SMC3 form a high-affinity heterodimer, which provides an open backbone of the cohesin ring, to be closed by a kleisin protein. RNAi mediated knock-down of either one heterodimer partner, SMC1 or SMC3, is expected to cause very similar if not identical phenotypes. However, we observed highly distinct, protein-specific phenotypes.

Interplay between neural-cadherin and vascular endothelial-cadherin in breast cancer progression.

Introduction: Deregulation of cadherin expression, in particular the loss of epithelial (E)-cadherin and gain of neural (N)-cadherin, has been implicated in carcinoma progression. We previously showed that endothelial cell-specific vascular endothelial (VE)-cadherin can be expressed aberrantly on tumor cells both in human breast cancer and in experimental mouse mammary carcinoma. Functional analyses revealed that VE-cadherin promotes tumor cell proliferation and invasion by stimulating transforming growth factor (TGF)-β signaling.

Genetic manipulation of endothelial cells by viral vectors.

The need for uncovering molecular mechanisms in endothelial cell biology has tremendously increased in the last decades as it became more and more clear that the endothelium is an important target in nearly all diseases and treatments (drug delivery) and plays a central role in regeneration processes. One of the critical methods generally applied in cell biology research to uncover structural and functional aspects is the modulation of protein expression by over-expression, expression of mutant variants or gene silencing. This strategy, however, requires genetic manipulation of the respective cells.

Vascular endothelial cadherin promotes breast cancer progression via transforming growth factor beta signaling.

Epithelial-to-mesenchymal transition (EMT) is an important event during carcinoma progression and leads to increased tumor cell malignancy. Here, we show that vascular endothelial (VE)-cadherin is induced during EMT in mammary tumor cells and is aberrantly expressed in invasive human breast carcinomas. VE-cadherin enhanced the capacity of fibroblastoid tumor cells to proliferate, form cord-like invasive structures, and adhere to endothelial cells, characteristics that are key contributors to their increased malignancy and metastatic potential.