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[PERSPECTIVES] The Funding Channels of Geroscience
This review examines the interconnected channels of government, individual, and corporate funding for geroscience. A sometimes-slow flow of federal and philanthropic funding over 50 years is now becoming sufficient to understand how the processes of aging drive disease. The amount has not yet been enough to push the benefits of geroscience into new therapeutics, but that is poised to change. Prominent billionaires, venture capitalists, and new foundations are investing billions in researching approaches for preventing, delaying, or curing the chronic diseases of older people; major pharmaceutical companies are poised to jo...
Source: Cold Spring Harbor perspectives in medicine - January 3, 2023 Category: Research Authors: Lederman, S. Tags: Aging PERSPECTIVES Source Type: research

[PERSPECTIVES] Platelets and (Lymph)angiogenesis
The formation of new blood and lymphatic vessels is essential for both the development of multicellular organisms and (patho)physiological processes like wound repair and tumor growth. In the 1990s, circulating blood platelets were first postulated to regulate tumor angiogenesis by interacting with the endothelium and releasing angiogenic regulators from specialized α granules. Since then, many studies have validated the contributions of platelets to tumor angiogenesis, while uncovering novel roles for platelets in other angiogenic processes like wound resolution and retinal vascular disease. Although the majority of...
Source: Cold Spring Harbor perspectives in medicine - January 3, 2023 Category: Research Authors: Roweth, H. G., Battinelli, E. M. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Signal Transduction and Gene Regulation in the Endothelium
Extracellular signals act on G-protein-coupled receptors (GPCRs) to regulate homeostasis and adapt to stress. This involves rapid intracellular post-translational responses and long-lasting gene-expression changes that ultimately determine cellular phenotype and fate changes. The lipid mediator sphingosine 1-phosphate (S1P) and its receptors (S1PRs) are examples of well-studied GPCR signaling axis essential for vascular development, homeostasis, and diseases. The biochemical cascades involved in rapid S1P signaling are well understood. However, gene-expression regulation by S1PRs are less understood. In this review, we foc...
Source: Cold Spring Harbor perspectives in medicine - January 3, 2023 Category: Research Authors: Levesque, M. V., Hla, T. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] From Life Span to Health Span: Declaring "Victory" in the Pursuit of Human Longevity
A difficult dilemma has presented itself in the current era. Modern medicine and advances in the medical sciences are tightly focused on a quest to find ways to extend life—without considering either the consequences of success or the best way to pursue it. From the perspective of physicians treating their patients, it makes sense to help them overcome immediate health challenges, but further life extension in increasingly more aged bodies will expose the saved population to an elevated risk of even more disabling health conditions associated with aging. Extended survival brought forth by innovations designed to trea...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2022 Category: Research Authors: Olshansky, S. J. Tags: Aging PERSPECTIVES Source Type: research

[PERSPECTIVES] Buttons and Zippers: Endothelial Junctions in Lymphatic Vessels
Button-like junctions are discontinuous contacts at the border of oak-leaf-shaped endothelial cells of initial lymphatic vessels. These junctions are distinctively different from continuous zipper-like junctions that create the endothelial barrier in collecting lymphatics and blood vessels. Button junctions are point contacts, spaced about 3 µm apart, that border valve-like openings where fluid and immune cells enter lymphatics. In intestinal villi, openings between button junctions in lacteals also serve as entry routes for chylomicrons. Like zipper junctions that join endothelial cells, buttons consist of adherens ...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2022 Category: Research Authors: Baluk, P., McDonald, D. M. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Human Endothelial Colony-Forming Cells
Endothelial colony-forming cells (ECFCs) are progenitor cells that can give rise to colonies of highly proliferative vascular endothelial cells (ECs) with clonal expansion and in vivo blood vessel–forming potential. More than two decades ago, the identification of ECFCs in human peripheral blood created tremendous opportunities as having a clinically accessible source of autologous ECs could facilitate meaningful therapies with the potential to impact multiple vascular diseases. Nevertheless, until recently, the field of endothelial progenitor cells has been plagued with ambiguities and controversies, and reaching a ...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2022 Category: Research Authors: Melero-Martin, J. M. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Evolutionary Approaches in Aging Research
While evolutionary explanations for aging have been widely acknowledged, the application of evolutionary principles to the practice of aging research has, until recently, been limited. Aging research has been dominated by studies of populations in evolutionarily novel industrialized environments and by use of short-lived animal models that are distantly related to humans. In this review, I address several emerging areas of "evolutionarily relevant" aging research, which provide a valuable complement to conventional biomedical research on aging. Nonhuman primates offer particular value as both translational and comparative ...
Source: Cold Spring Harbor perspectives in medicine - November 1, 2022 Category: Research Authors: Emery Thompson, M. Tags: Aging PERSPECTIVES Source Type: research

[PERSPECTIVES] Endothelial Cell Fate Determination: A Top Notch Job in Vascular Decision-Making
We describe mechanisms that control EC fate at specific steps in these processes, with an emphasis on the role of the Notch signaling pathway. Specific EC fate determination steps that are highlighted are tip/stalk selection during sprouting angiogenesis, venous-arterial specification, arteriogenesis, lymphatic vessel specification, and lymphatic valve formation. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - November 1, 2022 Category: Research Authors: Naiche, L. A., Villa, S. R., Kitajewski, J. K. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] The Beauty and Complexity of Blood Vessel Patterning
This review highlights new concepts in vascular patterning in the last 10 years, with emphasis on its beauty and complexity. Endothelial cell signaling pathways that respond to molecular or mechanical signals are described, and examples of vascular patterning that use these pathways in brain, skin, heart, and kidney are highlighted. The pathological consequences of patterning loss are discussed in the context of arteriovenous malformations (AVMs), and prospects for the next 10 years presented. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - November 1, 2022 Category: Research Authors: Bautch, V. L., Mukouyama, Y.-s. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Chromatin Variants Reveal the Genetic Determinants of Oncogenesis in Breast Cancer
Breast cancer presents as multiple distinct disease entities. Each tumor harbors diverse cell populations defining a phenotypic heterogeneity that impinges on our ability to treat patients. To date, efforts mainly focused on genetic variants to find drivers of inter- and intratumor phenotypic heterogeneity. However, these efforts have failed to fully capture the genetic basis of breast cancer. Through recent technological and analytical approaches, the genetic basis of phenotypes can now be decoded by characterizing chromatin variants. These variants correspond to polymorphisms in chromatin states at DNA sequences that ser...
Source: Cold Spring Harbor perspectives in medicine - October 3, 2022 Category: Research Authors: Bahl, S., Carroll, J. S., Lupien, M. Tags: Breast Cancer: From Fundamental Biology to Therapeutic Strategies PERSPECTIVES Source Type: research

[PERSPECTIVES] Leukocyte Trafficking in Lymphatic Vessels
To ensure proper immune function, most leukocytes constantly move within tissues or between them using the blood and lymphatic vessels as transport routes. While afferent lymphatic vessels transfer leukocytes from peripheral tissues to draining lymph nodes (dLNs), efferent lymphatics return lymphocytes from LNs back into the blood vascular circulation. Over the last decades, great progress has been made in our understanding of leukocyte migration into and within the lymphatic compartment, leading to the approval of new drugs targeting this process. In this review, we first introduce the anatomy of the lymphatic vasculature...
Source: Cold Spring Harbor perspectives in medicine - October 3, 2022 Category: Research Authors: Bauer, A., Tatliadim, H., Halin, C. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Endothelialitis, Microischemia, and Intussusceptive Angiogenesis in COVID-19
COVID-19 has been associated with a range of illness severity—from minimal symptoms to life-threatening multisystem organ failure. The severe forms of COVID-19 appear to be associated with an angiocentric or vascular phase of the disease. In studying autopsy patients succumbing to COVID-19, we found alveolar capillary microthrombi were 9 times more common in COVID-19 than in comparable patients with influenza. Corrosion casting of the COVID-19 microcirculation has revealed microvascular distortion, enhanced bronchial circulation, and striking increases in intussusceptive angiogenesis. In patients with severe COVID-19...
Source: Cold Spring Harbor perspectives in medicine - October 3, 2022 Category: Research Authors: Mentzer, S. J., Ackermann, M., Jonigk, D. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Gene Therapy for Rhodopsin Mutations
Mutations in RHO, the gene for rhodopsin, account for a large fraction of autosomal-dominant retinitis pigmentosa (adRP). Patients fall into two clinical classes, those with early onset, pan retinal photoreceptor degeneration, and those who experience slowly progressive disease. The latter class of patients are candidates for photoreceptor-directed gene therapy, while former may be candidates for delivery of light-responsive proteins to interneurons or retinal ganglion cells. Gene therapy for RHO adRP may be targeted to the mutant gene at the DNA or RNA level, while other therapies preserve the viability of photoreceptors ...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2022 Category: Research Authors: Lewin, A. S., Smith, W. C. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Lymphatic Tissue and Organ Engineering for In Vitro Modeling and In Vivo Regeneration
The lymphatic system has an important role in maintaining fluid homeostasis and transporting immune cells and biomolecules, such as dietary fat, metabolic products, and antigens in different organs and tissues. Therefore, impaired lymphatic vessel function and/or lymphatic vessel deficiency can lead to numerous human diseases. The discovery of lymphatic endothelial markers and prolymphangiogenic growth factors, along with a growing number of in vitro and in vivo models and technologies has expedited research in lymphatic tissue and organ engineering, advancing therapeutic strategies. In this article, we describe lymphatic ...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2022 Category: Research Authors: Kolarzyk, A. M., Wong, G., Lee, E. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Notch Signaling in Vascular Endothelial and Mural Cell Communications
The Notch signaling pathway is a highly versatile and evolutionarily conserved mechanism with an important role in cell fate determination. Notch signaling plays a vital role in vascular development, regulating several fundamental processes such as angiogenesis, arterial/venous differentiation, and mural cell investment. Aberrant Notch signaling can result in severe vascular phenotypes as observed in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Alagille syndrome. It is known that vascular endothelial cells and mural cells interact to regulate vessel formation, cel...
Source: Cold Spring Harbor perspectives in medicine - September 1, 2022 Category: Research Authors: O'Hare, M., Arboleda-Velasquez, J. F. Tags: Angiogenesis PERSPECTIVES Source Type: research