Endothelial Pim3 kinase protects the vascular barrier during lung metastasis.

Endothelial cells (ECs) form a tissue-specific barrier for disseminating cancer cells in distant organs. However, the molecular regulation of the ECs in the metastatic niche remains unclear. Here, we analyze using scRNA-Seq, the transcriptional reprogramming of lung ECs six hours after the arrival of melanoma cells in mouse lungs.

Drugs for dyslipidaemia: the legacy effect of the Scandinavian Simvastatin Survival Study (4S).

Since the discovery of statins and the Scandinavian Simvastatin Survival Study (4S) results three decades ago, remarkable advances have been made in the treatment of dyslipidaemia, a major risk factor for atherosclerotic cardiovascular disease. Safe and effective statins remain the cornerstone of therapeutic approach for this indication, including for children with genetic dyslipidaemia, and are one of the most widely prescribed drugs in the world. However, despite the affordability of generic statins, they remain underutilised worldwide.

Specialized post-arterial capillaries facilitate adult bone remodelling.

The vasculature of the skeletal system is crucial for bone formation, homoeostasis and fracture repair, yet the diversity and specialization of bone-associated vessels remain poorly understood. Here we identify a specialized type of post-arterial capillary, termed type R, involved in bone remodelling. Type R capillaries emerge during adolescence around trabecular bone, possess a distinct morphology and molecular profile, and are associated with osteoprogenitors and bone-resorbing osteoclasts.

Multiparameter imaging reveals clinically relevant cancer cell-stroma interaction dynamics in head and neck cancer.

Epithelial tumors are characterized by abundant inter- and intra-tumor heterogeneity, which complicates diagnostics and treatment. The contribution of cancer-stroma interactions to this heterogeneity is poorly understood. Here, we report a paradigm to quantify phenotypic diversity in head and neck squamous cell carcinoma (HNSCC) with single-cell resolution.

Heart-healthy diets including phytostanol ester consumption to reduce the risk of atherosclerotic cardiovascular diseases. A clinical review.

The risk of atherosclerotic cardiovascular diseases (ASCVDs) can be reduced by lowering low-density lipoprotein cholesterol (LDL-C) concentrations. Nevertheless, ASCVDs still cause most deaths worldwide. Here, we discuss the prevention of ASCVD and the event risk with a focus on heart-healthy diets, i.

Distinct molecular profiles and shared drug vulnerabilities in pancreatic metastases of renal cell carcinoma.

Clear-cell renal cell carcinoma (ccRCC) is the most common origin of pancreatic metastases (PM). Distinct genomic aberrations, favorable prognosis, and clinical observations on high angiogenesis, and succeeding tyrosine kinase inhibitor (TKI) sensitivity have been reported in PM-ccRCC. However, no functional or single-cell studies have been conducted thus far.

Overactive mitochondrial DNA replication disrupts perinatal cardiac maturation.

High mitochondrial DNA (mtDNA) amount has been reported to be beneficial for resistance and recovery of metabolic stress, while increased mtDNA synthesis activity can drive aging signs. The intriguing contrast of these two mtDNA boosting outcomes prompted us to jointly elevate mtDNA amount and frequency of replication in mice. We report that high activity of mtDNA synthesis inhibits perinatal metabolic maturation of the heart.

Treatment with APAC, a dual antiplatelet anticoagulant heparin proteoglycan mimetic, limits early collar-induced carotid atherosclerotic plaque development in Apoe mice.

Background And Aims: Mast cell-derived heparin proteoglycans (HEP-PG) can be mimicked by bioconjugates carrying antithrombotic and anti-inflammatory properties. The dual antiplatelet and anticoagulant (APAC) construct administered, either locally or intravenously (i.v.

Genetic targeting of lymphatic endothelial cells in mice: current strategies and future perspectives.

Lymphatic vessels within different organs have diverse developmental origins, depend on different growth factor signaling pathways for their development and maintenance, and display notable tissue-specific adaptations that contribute to their roles in normal physiology and in various diseases. Functional studies on the lymphatic vasculature rely extensively on the use of mouse models that allow selective gene targeting of lymphatic endothelial cells (LECs). Here, we discuss LEC diversity and provide an overview of some of the commonly used LEC-specific inducible Cre lines and induction protocols, outlining essential experimental parameters and their implications.

Statins for the prevention of cardiovascular events associated with avian influenza: the COVID-19 pandemic as a reference.

There is growing concern that the severe respiratory disease in birds (avian influenza or 'bird flu') caused by the H5N1 influenza virus, might potentially spread more widely to humans and cause a pandemic. Here we discuss clinical issues related to human infections by the highly pathogenic H5N1 subtype of the avian influenza A virus and make a clinical comparison with recent information obtained from studies of SARS-CoV-2 infection. Firstly, we consider the potential increase in cardiovascular events in humans infected with the H5N1 virus.

Sustained meningeal lymphatic vessel atrophy or expansion does not alter Alzheimer's disease-related amyloid pathology.

Discovery of meningeal lymphatic vessels (LVs) in the dura mater, also known as dural LVs (dLVs) that depend on vascular endothelial growth factor C expression, has raised interest in their possible involvement in Alzheimer's disease (AD). Here we find that in the APdE9 and 5xFAD mouse models of AD, dural amyloid-β (Aβ) is confined to blood vessels and dLV morphology or function is not altered. The induction of sustained dLV atrophy or hyperplasia in the AD mice by blocking or overexpressing vascular endothelial growth factor C, impaired or improved, respectively, macromolecular cerebrospinal fluid (CSF) drainage to cervical lymph nodes.

Inhibitor development according to concentrate after 50 exposure days in severe hemophilia: data from the European HAemophilia Safety Surveillance (EUHASS).

Background: Patients with hemophilia have a life-long risk of developing neutralizing antibodies (inhibitors) against clotting factor concentrates. After the first 50 exposure days (EDs), ie, in previously treated patients (PTPs), data on inhibitor development are limited.

Objectives: To report inhibitor development according to factor (F)VIII or FIX concentrate use in PTPs with severe hemophilia A and B.

The relationship between the secondary vascular system and the lymphatic vascular system in fish.

New technologies have resulted in a better understanding of blood and lymphatic vascular heterogeneity at the cellular and molecular levels. However, we still need to learn more about the heterogeneity of the cardiovascular and lymphatic systems among different species at the anatomical and functional levels. Even the deceptively simple question of the functions of fish lymphatic vessels has yet to be conclusively answered.

Deletion of the Murine Ortholog of the Human 9p21.3 Locus Leads to Insulin Resistance and Obesity in Hypercholesterolemic Mice.

The 9p21.3 genomic locus is a hot spot for disease-associated single-nucleotide polymorphisms (SNPs), and its strongest associations are with coronary artery disease (CAD). The disease-associated SNPs are located within the sequence of a long noncoding RNA ANRIL, which potentially contributes to atherogenesis by regulating vascular cell stress and proliferation, but also affects pancreatic β-cell proliferation.

Spatially targeted chemokine exocytosis guides transmigration at lymphatic endothelial multicellular junctions.

Migrating cells preferentially breach and integrate epithelial and endothelial monolayers at multicellular vertices. These sites are amenable to forces produced by the migrating cell and subsequent opening of the junctions. However, the cues that guide migrating cells to these entry portals, and eventually drive the transmigration process, are poorly understood.

iSuRe-HadCre is an essential tool for effective conditional genetics.

Methods for modifying gene function at high spatiotemporal resolution in mice have revolutionized biomedical research, with Cre-loxP being the most widely used technology. However, the Cre-loxP technology has several drawbacks, including weak activity, leakiness, toxicity, and low reliability of existing Cre-reporters. This is mainly because different genes flanked by loxP sites (floxed) vary widely in their sensitivity to Cre-mediated recombination.

The Impact of VEGF-C-Induced Dural Lymphatic Vessel Growth on Ischemic Stroke Pathology.

Timely relief of edema and clearance of waste products, as well as promotion of anti-inflammatory immune responses, reduce ischemic stroke pathology, and attenuate harmful long-term effects post-stroke. The discovery of an extensive and functional lymphatic vessel system in the outermost meningeal layer, dura mater, has opened up new possibilities to facilitate post-stroke recovery by inducing dural lymphatic vessel (dLV) growth via a single injection of a vector encoding vascular endothelial growth factor C (VEGF-C). In the present study, we aimed to improve post-stroke outcomes by inducing dLV growth in mice.