Cold Spring Harbor perspectives in medicine This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

[PERSPECTIVES] Lymphatic Vascular Permeability
Blood vessels have a regulated permeability to fluid and solutes, which allows for the delivery of nutrients and signaling molecules to all cells in the body, a process essential to life. The lymphatic vasculature is the second network of vessels in the body, making up part of the immune system, yet is not typically thought of as having a permeability to fluid and solute. However, the major function of the lymphatic vasculature is to regulate tissue fluid balance to prevent edema, so lymphatic vessels must be permeable to absorb and transport fluid efficiently. Only recently were lymphatic vessels discovered to be permeabl...
Source: Cold Spring Harbor perspectives in medicine - August 15, 2022 Category: Research Authors: Scallan, J. P., Jannaway, M. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] MicroRNAs in Mechanical Homeostasis
Mechanical variables such as stiffness, stress, strain, and fluid shear stress are central to tissue functions, thus, must be maintained within the proper range. Mechanics are especially important in the cardiovascular system and lung, the functions of which are essentially mechanical. Mechanical homeostasis is characterized by negative feedback in which deviations from the optimal value or set point activates mechanisms to return the system to the correct range. In chronic diseases, homeostatic mechanisms are generally overcome or replaced with positive feedback loops that promote disease progression. Recent work has show...
Source: Cold Spring Harbor perspectives in medicine - August 15, 2022 Category: Research Authors: Herrera, J. A., Schwartz, M. A. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Lymphatics in Cardiovascular Physiology
The lymphatic vessels play an essential role in maintaining immune and fluid homeostasis and in the transport of dietary lipids. The discovery of lymphatic endothelial cell–specific markers facilitated the visualization and mechanistic analysis of lymphatic vessels over the past two decades. As a result, lymphatic vessels have emerged as a crucial player in the pathogenesis of several cardiovascular diseases, as demonstrated by worsened disease progression caused by perturbations to lymphatic function. In this review, we discuss the major findings on the role of lymphatic vessels in cardiovascular diseases such as hy...
Source: Cold Spring Harbor perspectives in medicine - August 15, 2022 Category: Research Authors: Balasubbramanian, D., Mitchell, B. M. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Molecular Mechanisms Driving Lymphedema and Other Lymphatic Anomalies
Lymphatic vasculature regulates fluid homeostasis by absorbing interstitial fluid and returning it to blood. Lymphatic vasculature is also critical for lipid absorption and inflammatory response. Lymphatic vasculature is composed of lymphatic capillaries, collecting lymphatic vessels, lymphatic valves, and lymphovenous valves. Defects in any of these structures could lead to lymphatic anomalies such as lymphedema, cystic lymphatic malformation, and Gorham–Stout disease. Basic research has led to a deeper understanding of the stepwise development of the lymphatic vasculature. VEGF-C and shear stress signaling pathways...
Source: Cold Spring Harbor perspectives in medicine - July 29, 2022 Category: Research Authors: Geng, X., Srinivasan, R. S. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Mechanisms Regulating T Cell-Endothelial Cell Interactions
T-cell interaction with the endothelial cells lining the vessel wall is a necessary step in the inflammatory response that allows T cells to extravasate from the circulation and migrate to sites of infectious or sterile inflammation. On one hand, the vascular endothelium is activated and, as a result, switches from an anti-adhesive to a pro-adhesive state, allowing adhesion of T cells and other leukocytes. On the other hand, T cells express ligands of endothelial adhesion molecules to sustain these interactions that eventually result in T-cell extravasation into sites of inflammation. A better understanding of the central ...
Source: Cold Spring Harbor perspectives in medicine - July 29, 2022 Category: Research Authors: Alcaide, P. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Endothelial Cell Differentiation and Hemogenic Specification
Formation of the vasculature is a critical step within the developing embryo and its disruption causes early embryonic lethality. This complex process is driven by a cascade of signaling events that controls differentiation of mesodermal progenitors into primordial endothelial cells and their further specification into distinct subtypes (arterial, venous, hemogenic) that are needed to generate a blood circulatory network. Hemogenic endothelial cells give rise to hematopoietic stem and progenitor cells that generate all blood cells in the body during embryogenesis and postnatally. We focus our discussion on the regulation o...
Source: Cold Spring Harbor perspectives in medicine - July 29, 2022 Category: Research Authors: Aragon, J. W., Hirschi, K. K. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] From Bench to Bedside--Delivering Gene Therapy for Leber Hereditary Optic Neuropathy
Leber hereditary optic neuropathy (LHON) is a rare, maternally inherited mitochondrial disorder that presents with severe bilateral sequential vision loss, due to the selective degeneration of retinal ganglion cells (RGCs). Since the mitochondrial genetic basis for LHON was uncovered in 1988, considerable progress has been made in understanding the pathogenetic mechanisms driving RGC loss, which has enabled the development of therapeutic approaches aimed at mitigating the underlying mitochondrial dysfunction. In this review, we explore the genetics of LHON, from bench to bedside, focusing on the pathogenetic mechanisms and...
Source: Cold Spring Harbor perspectives in medicine - July 21, 2022 Category: Research Authors: Chen, B. S., Yu-Wai-Man, P. Tags: Retinal Disorders: Genetic Approaches to Diagnosis and Treatment PERSPECTIVES Source Type: research

[PERSPECTIVES] Beyond Static Pipes: Mechanisms and In Vitro Models of Vascular Aging
The vascular system is a key player for the maintenance of healthy tissues, suggesting how the physiological decline of blood vessel functionality during aging could be a major contributor of organ degeneration. While basic research studies have begun to pinpoint potential mechanisms of vascular aging, it is now critical to translate them into therapeutically relevant options. Microphysiological systems represent a powerful tool to precisely control which combinations of stimuli are provided to in vitro reconstructed blood vessels and to analyze their functional consequences. After highlighting key aspects of vascular agin...
Source: Cold Spring Harbor perspectives in medicine - July 21, 2022 Category: Research Authors: Hetzer, M. W., Bersini, S. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Endothelial Lipid Metabolism
Endothelial cells (ECs) line all vessels of all vertebrates and are fundamental to organismal metabolism. ECs rely on their metabolism both to transport nutrients in and out of underlying parenchyma, and to support their own cellular activities, including angiogenesis. ECs primarily consume glucose, and much is known of how ECs transport and consume glucose and other carbohydrates. In contrast, how lipids are transported, and the role of lipids in normal EC function, has garnered less attention. We review here recent developments on the role of lipids in endothelial metabolism, with a focus on lipid uptake and transport in...
Source: Cold Spring Harbor perspectives in medicine - July 21, 2022 Category: Research Authors: Kim, B., Arany, Z. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] The Evolution and Biology of SARS-CoV-2 Variants
Our understanding of the still unfolding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic would have been extremely limited without the study of the genetics and evolution of this new human coronavirus. Large-scale genome-sequencing efforts have provided close to real-time tracking of the global spread and diversification of SARS-CoV-2 since its entry into the human population in late 2019. These data have underpinned analysis of its origins, epidemiology, and adaptations to the human population: principally immune evasion and increasing transmissibility. SARS-CoV-2, despite being a new human pathogen,...
Source: Cold Spring Harbor perspectives in medicine - May 27, 2022 Category: Research Authors: Telenti, A., Hodcroft, E. B., Robertson, D. L. Tags: COVID-19 PERSPECTIVES Source Type: research

[PERSPECTIVES] Lymphedema and Obesity
Lymphedema results from inadequate lymphatic function. Extreme obesity can cause lower extremity lymphedema, termed "obesity-induced lymphedema (OIL)." OIL is a form of secondary lymphedema that may occur once an individual's body mass index (BMI) exceeds 40. The risk of lymphatic dysfunction increases with elevated BMI and is almost universal once BMI exceeds 60. Obesity has a negative impact on lymphatic density in subcutaneous tissue, lymphatic endothelial cell proliferation, lymphatic leakiness, collecting-vessel pumping capacity, and clearance of macromolecules. Lymphatic fluid unable to be taken up by lymphatic vesse...
Source: Cold Spring Harbor perspectives in medicine - May 27, 2022 Category: Research Authors: Sudduth, C. L., Greene, A. K. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Endothelial Connexins in Developmental and Pathological Angiogenesis
Connexins (Cxs) constitute a large family of transmembrane proteins that form gap junction channels, which enable the direct transfer of small signaling molecules from cell to cell. In blood vessels, Cx channels allow the endothelial cells (ECs) to respond to external and internal cues as a whole and, thus, contribute to the maintenance of vascular homeostasis. While the role of Cxs has been extensively studied in large arteries, a growing body of evidence suggests that they also play a role in the formation of microvascular networks. Since the formation of new blood vessels requires the coordinated response of ECs to exte...
Source: Cold Spring Harbor perspectives in medicine - May 27, 2022 Category: Research Authors: Haefliger, J.-A., Meda, P., Alonso, F. Tags: Angiogenesis PERSPECTIVES Source Type: research

[PERSPECTIVES] Tumor Immunology and Immunotherapy of Non-Small-Cell Lung Cancer
Historically, non-small-cell lung cancer (NSCLC) has been regarded as a nonimmunogenic tumor; however, recent studies have shown that NSCLCs are among the most responsive cancers to monoclonal antibody immune checkpoint inhibitors (ICIs). ICIs have dramatically improved clinical outcomes for a subset of patients (~20%) with locally advanced and metastatic NSCLC, and they have also demonstrated promise as neoadjuvant therapy for early-stage resectable disease. Nevertheless, the majority of patients with NSCLC are refractory to ICIs for reasons that are poorly understood. Thus, major questions are: how do we initially identi...
Source: Cold Spring Harbor perspectives in medicine - May 27, 2022 Category: Research Authors: Cascone, T., Fradette, J., Pradhan, M., Gibbons, D. L. Tags: Lung Cancer: Disease Biology and Its Potential for Clinical Translation PERSPECTIVES Source Type: research

[PRIMER] Mendelian Randomization
Mendelian randomization borrows statistical techniques from economics to allow researchers to analyze the effects of the environment, drug treatments, and other factors on human biology and disease. Taking advantage of the fact that genetic variation is randomized among children from the same parents, it allows genetic variants known to influence factors like alcohol consumption or low-density lipoprotein (LDL) levels to be used as instrumental variables that can disentangle the effects of these factors on outcomes such as pregnancy or cardiovascular disease, respectively. There are caveats to analyses using Mendelian rand...
Source: Cold Spring Harbor perspectives in medicine - May 17, 2022 Category: Research Authors: Birney, E. Tags: Combining Human Genetics and Causal Inference to Understand Human Disease and Development PRIMER Source Type: research

[PERSPECTIVES] Lung Cancer Stem Cells and Their Clinical Implications
It is now widely accepted that stem cells exist in various cancers, including lung cancer, which are referred to as cancer stem cells (CSCs). CSCs are defined in this context as the subset of tumor cells with the ability to form tumors in serial transplantation and cloning assays and form tumors at metastatic sites. Mouse models of lung cancer have shown that lung CSCs reside in niches that are essential for the maintenance of stemness, plasticity, enable antitumor immune evasion, and provide metastatic potential. Similar to normal lung stem cells, Notch, Wnt, and the Hedgehog signaling cascades have been recruited by the ...
Source: Cold Spring Harbor perspectives in medicine - May 17, 2022 Category: Research Authors: Rowbotham, S. P., Goruganthu, M. U. L., Arasada, R. R., Wang, W. Z., Carbone, D. P., Kim, C. F. Tags: Lung Cancer: Disease Biology and Its Potential for Clinical Translation PERSPECTIVES Source Type: research