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Purpose of Review: Single-cell RNA sequencing (scRNA-seq) can capture the transcriptional profile of thousands of individual cells concurrently from complex tissues and with remarkable resolution. Either with the goal of seeking information about distinct cell subtypes or responses to a stimulus, the approach has provided robust information and promoted impressive advances in cardiovascular research. The goal of this review is to highlight strategies and approaches to leverage this technology and bypass potential caveats related to evaluation of the vascular cells., Recent Findings: As the most recent technological development, details associated with experimental strategies, analysis, and interpretation of scRNA-seq data are still being discussed and scrutinized by investigators across the vascular field. Compilation of this information is valuable for those using the technology but particularly important to those about to start utilizing scRNA-seq to seek transcriptome information of vascular cells., Summary: As our field progresses to catalog transcriptomes from distinct vascular beds, it is undeniable that scRNA-seq technology is here to stay. Sharing approaches to improve the quality of cell dissociation procedures, analysis, and a consensus of best practices is critical as information from this powerful experimental platform continues to emerge., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: The well recognized plasticity and diversity, typical of monocytes and macrophages have recently been expanded by the knowledge that additional macrophage lineages originated directly from embryonic progenitors, populate and establish residency in all tissues examined so far. This review aims to summarize our current understanding on the diversity of monocyte/macrophage subtypes associated with the vasculature, their specific origins, and nature of their cross-talk with the endothelium., Recent Findings: Taking stock of the many interactions between the endothelium and monocytes/macrophages reveals a far more intricate and ever-growing depth. In addition to circulating and surveilling the endothelium, monocytes can specifically be differentiated into patrolling cells that crawl on the surface of the endothelium and promote homeostasis. The conversion of classical to patrolling is endothelium-dependent uncovering an important functional link. In addition to patrolling cells, the endothelium also recruits and harbor an intimal-resident myeloid population that resides in the tunica intima in the absence of pathological insults. Moreover, the adventitia is populated with resident macrophages that support blood vessel integrity and prevent fibrosis., Summary: The last few years have witnessed a significant expansion in our knowledge of the many subtypes of monocytes and macrophages and their corresponding functional interactions with the vascular wall. In addition to surveying the endothelium for opportunities of diapedeses, monocyte and macrophages take residence in both the intima (as patrolling or resident) and in the adventitia. Their contributions to vascular function are broad and critical to homeostasis, regeneration, and expansion.

Purpose of Review: Microvascular ischemic disease of the brain is a common cause of cognitive impairment and dementia, particularly in the context of preexisting cardiovascular risk factors and aging. This review summarizes our current understanding of the emerging molecular themes that underlie progressive and irreparable vascular disease leading to neuronal tissue injury and dementia., Recent Findings: Cardiometabolic risk factors including diabetes and hypertension are known to contribute to vascular disease. Currently, the impact of these risk factors on the integrity and function of the brain vasculature has been target of intense investigation. Molecularly, the consequences associated with these risk factors indicate that reactive oxygen species are strong contributors to cerebrovascular dysfunction and injury. In addition, genetic linkage analyses have identified penetrant monogenic causes of vascular dementia. Finally, recent reports begun to uncover a large number of polymorphisms associated with a higher risk for cerebrovascular disease., Summary: A comprehensive picture of key risk factors and genetic predispositions that contribute to brain microvascular disease and result in vascular dementia is starting to emerge. Understanding their relationships and cross-interactions will significantly aid in the development of preventive and intervention strategies for this devastating condition.

Purpose of Review: The formation of a hierarchical vascular network is a complex process that requires precise temporal and spatial integration of several signaling pathways. Amongst those, Notch has emerged as a key regulator of multiple steps that expand from endothelial sprouting to arterial specification and remains relevant in the adult. This review aims to summarize major concepts and rising hypotheses on the role of Notch signaling in the endothelium., Recent Findings: A wealth of new information has helped to clarify how Notch signaling cooperates with other pathways to orchestrate vascular morphogenesis, branching, and function. Endothelial vascular endothelial growth factor, C-X-C chemokine receptor type 4, and nicotinamide adenine dinucleotide phosphate oxidase 2 have been highlighted as key regulators of the pathway. Furthermore, blood flow forces during vascular development induce Notch1 signaling to suppress endothelial cell proliferation, enhance barrier function, and promote arterial specification. Importantly, Notch1 has been recently recognized as an endothelial mechanosensor that is highly responsive to the level of shear stress to enable differential Notch activation in distinct regions of the vessel wall and suppress inflammation., Summary: Although it is well accepted that the Notch signaling pathway is essential for vascular morphogenesis, its contributions to the homeostasis of adult endothelium were uncovered only recently. Furthermore, its exquisite regulation by flow and impressive interface with multiple signaling pathways indicates that Notch is at the center of a highly interactive web that integrates both physical and chemical signals to ensure vascular stability.

Purpose of Review: This review offers a concise summary of the most recent experimental advances in vascular development using the mouse as a model organism., Recent Findings: Recent mouse studies have revealed a spread of phenotypic diversity between endothelia of distinct developmental origins and organs. For example, expression of unique transcription factors distinguishes hemogenic from nonhemogenic endothelium within the same vessel. Vasculature of the brain is particularly susceptible to endothelial malformations due to combinatorial germline and somatic mutations; surprisingly these mutations can afflict the endothelium by either cell autonomous or paracrine effects. Mutant mice have been used to understand how multiple signaling pathways integrate and refine cellular responses. In particular, we learned how VEGFR3 regulates Notch signaling and EphrinB2 coordinates VEGFR2 responses. The regulation of Prox1 by miR181 highlighted the contribution of microRNAs in the induction of lymphatic endothelium. Information gained on heterotypic interactions has further clarified the influence of blood vessels on the morphogenesis of parenchyma and contributed to our understanding of organ-specific endothelial differentiation. Finally, mouse models have uncovered endothelial cell polarity as a keystone for successful vascular lumenization., Summary: Our understanding of the process of vascular development has gained significant refinement in the last two years and has clarified the origin of several disorders rooted in development.

Purpose of Review: In this mini-review, we have highlighted the recent breakthroughs in growth factor signaling that have made conceptual changes in our understanding of how blood vessels are formed., Recent Findings: Studies conducted over the past few years have focused on understanding the cell biology of vascular morphogenesis. The major themes include characterization of the different cell types that comprise a vascular sprout, as well as the regulatory influence of cell-cell and cell-matrix interactions on signaling outcomes. In addition, novel trends have emerged, including nonconventional ways in which vascular endothelial growth factor contributes to cell survival and metabolic balance., Summary: The growth of new capillary sprouts from a preexisting vascular network requires a highly coordinated cellular response to both growth factors and morphogens. This response is sensed and triggered by cell surface receptors responsible for the activation of an intracellular cascade that efficiently initiates migration and proliferation programs. While the molecular players that coordinate these effects have been identified, recent findings have expanded our understanding of how context, in particular cell-cell and cell-matrix interactions, affects endothelial cell responses to growth factors.

Purpose of Review: This review highlights recent developments in the role of the Notch signaling pathway during vascular morphogenesis, angiogenesis, and vessel homeostasis., Recent Findings: Studies conducted over the past 4 years have significantly advanced the understanding of the effect of Notch signaling on vascular development. Major breakthroughs have elucidated the role of Notch in arterial versus venular specification and have placed this pathway downstream of vascular endothelial growth factor., Summary: An emerging hallmark of the Notch signaling pathway is its nearly ubiquitous participation in cell fate decisions that affect several tissues, including epithelial, neuronal, hematopoietic, and muscle. The vascular compartment has been the latest addition to the list of tissues known to be regulated by Notch. Unraveling the contribution of Notch signaling to blood vessel formation has resulted principally from gain-of-function and loss-of-function experiments in mouse and zebrafish. During the past 4 years, these mechanistic studies have revealed that Notch is required for the successful completion of several steps during vascular morphogenesis and differentiation. In addition, the findings that Notch mutations are linked to some late-onset hereditary vascular pathologic conditions suggest the added contribution of this signaling pathway to vascular homeostasis.