endothelial cell and metabolism

Mitomycin C (MMC)-induced genotoxic stress can be considered to be a novel trigger of endothelial dysfunction and atherosclerosis-a leading cause of cardiovascular morbidity and mortality worldwide. Given the increasing genotoxic load on the human organism, the decryption of the molecular pathways underlying genotoxic stress-induced endothelial dysfunction could improve our understanding of the role of genotoxic stress in atherogenesis. Here, we performed a proteomic profiling of human coronary artery endothelial cells (HCAECs) and human internal thoracic endothelial cells (HITAECs) in vitro that were exposed to MMC to identify the biochemical pathways and proteins underlying genotoxic stress-induced endothelial dysfunction...

Vascular cognitive impairment and dementia (VCID) represents a broad spectrum of cognitive decline secondary to cerebral vascular aging and injury. It is the second most common type of dementia, and the prevalence continues to increase. Nuclear factor erythroid 2-related factor 2 (NRF2) is enriched in the cerebral vasculature and has diverse roles in metabolic balance, mitochondrial stabilization, redox balance, and anti-inflammation. In this review, we first briefly introduce cerebrovascular aging in VCID and the NRF2 pathway...

Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK) whose structural and regulatory features are distinct from those of conventional MAPKs, such as ERK1/2. Since its identification in 1991, the regulation, substrates and functions of ERK3 have remained largely unknown. However, recent years have witnessed a wealth of new findings about ERK3 signaling. Several important biological functions for ERK3 have been revealed, including its role in neuronal morphogenesis, inflammation, metabolism, endothelial cell tube formation and epithelial architecture...

Renal fibrosis, specifically tubulointerstitial fibrosis, represents the predominant pathological consequence observed in the context of progressive chronic kidney conditions. The pathogenesis of renal fibrosis encompasses a multifaceted interplay of mechanisms, including but not limited to interstitial fibroblast proliferation, activation, augmented production of extracellular matrix (ECM) components, and impaired ECM degradation. Notably, mitochondria, the intracellular organelles responsible for orchestrating biological oxidation processes in mammalian cells, assume a pivotal role within this intricate milieu...

Reelin, a large extracellular glycoprotein, plays critical roles in neuronal development and synaptic plasticity in the central nervous system (CNS). Recent studies have revealed non-neuronal functions of plasma Reelin in inflammation by promoting endothelial-leukocyte adhesion through its canonical pathway in endothelial cells (via ApoER2 acting on NF-κB), as well as in vascular tone regulation and thrombosis. In this study, we have investigated the safety and efficacy of selectively depleting plasma Reelin as a potential therapeutic strategy for chronic inflammatory diseases...

The blood-brain barrier (BBB) serves as a highly intricate and dynamic interface connecting the brain and the bloodstream, playing a vital role in maintaining brain homeostasis. BBB dysfunction has been associated with multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS); however, the role of the BBB in neurodegeneration is understudied. We developed an ALS patient-derived model of the BBB by using cells derived from 5 patient donors carrying C9ORF72 mutations. Brain microvascular endothelial-like cells (BMEC-like cells) derived from C9ORF72-ALS patients showed altered gene expression, compromised barrier integrity, and increased P-glycoprotein transporter activity...

OBJECTIVE: To investigate the potential changes of glucose metabolism and glucose transporter protein (GLUT) in the visual cortex of formally deprived amblyopic rats, as well as the effects of enriched environments on the levels of nerve conduction and glucose metabolism in the visual cortex of amblyopic rats. METHODS: 36 rats were randomly divided into three groups: CON + SE (n = 12), MD + SE (n = 12) and MD + EE (n = 12)...

Cadmium (Cd) is an environmental risk factor of cardiovascular diseases. Researchers have found that Cd exposure causes energy metabolic disorders in the heart decades ago. However, the underlying molecular mechanisms are still elusive. In this study, male C57BL/6 J mice were exposed to cadmium chloride (CdCl2 ) through drinking water for 4 weeks. We found that exposure to CdCl2 increased glucose uptake and utilization, and disrupted normal metabolisms in the heart. In vitro studies showed that CdCl2 specifically increased endothelial glucose uptake without affecting cardiomyocytic glucose uptake and endothelial fatty acid uptake...

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Others and our studies have shown that mechanical stresses (forces) including shear stress and cyclic stretch, occur in various pathological conditions, play significant roles in the development and progression of CVDs. Mitochondria regulate the physiological processes of cardiac and vascular cells mainly through adenosine triphosphate (ATP) production, calcium flux and redox control while promote cell death through electron transport complex (ETC) related cellular stress response...

Resident synoviocytes and synovial microvasculature, together with immune cells from circulation, contribute to pannus formation, the main pathological feature of rheumatoid arthritis (RA), leading to destruction of adjacent cartilage and bone. Seeds, fibroblast-like synoviocytes (FLSs), macrophages, dendritic cells (DCs), B cells, T cells and endothelial cells (ECs) seeds with high metabolic demands undergo metabolic reprogramming from oxidative phosphorylation to glycolysis in response to poor soil of RA synovium with hypoxia, nutrient deficiency and inflammatory stimuli...

Tumor microenvironment (TME) has been demonstrated to play a significant role in tumor initiation, progression, and metastasis. Cancer-associated fibroblasts (CAFs) are the major component of TME and exhibit heterogeneous properties in their communication with tumor cells. This heterogeneity of CAFs can be attributed to various origins, including quiescent fibroblasts, mesenchymal stem cells (MSCs), adipocytes, pericytes, endothelial cells, and mesothelial cells. Moreover, single-cell RNA sequencing has identified diverse phenotypes of CAFs, with myofibroblastic CAFs (myCAFs) and inflammatory CAFs (iCAFs) being the most acknowledged, alongside newly discovered subtypes like antigen-presenting CAFs (apCAFs)...

INTRODUCTION: The close association between cuproptosis and tumor immunity in triple-negative breast cancer (TNBC) allows its monitoring for predicting the prognosis of patients with TNBC. Nevertheless, the biological function and prognostic value of cuproptosis-related miRNAs and their target genes have not been reported. PURPOSE: To construct the miRNA and mRNA-based risk models associated with cuproptosis for patients with TNBC. METHODS: Comparison of expression levels for genes associated with cuproptosis was executed between patients in the normal individuals and the TCGA-TNBC cohort...

The non-neuronal cholinergic system of the cardiovascular system has recently gained attention because of its origin. The final product of this system is acetylcholine (ACh) not derived from the parasympathetic nervous system but from cardiomyocytes, endothelial cells, and immune cells. Accordingly, it is defined as an ACh synthesis system by non-neuronal cells. This system plays a dispensable role in the heart and cardiomyocytes, which is confirmed by pharmacological and genetic studies using murine models, such as models with the deletion of vesicular ACh transporter gene and modulation of the choline acetyltransferase (ChAT) gene...

The aim of the present study was to investigate retinal microcirculatory and functional metabolic changes in patients after they had recovered from a moderate to severe acute COVID-19 infection. Retinal perfusion was quantified using laser speckle flowgraphy. Oxygen saturation and retinal calibers were assessed with a dynamic vessel analyzer. Arterio-venous ratio (AVR) was calculated based on retinal vessel diameter data. Blood plasma samples underwent mass spectrometry-based multi-omics profiling, including proteomics, metabolomics and eicosadomics...

BACKGROUND/OBJECTIVES: We investigated whether dietary interventions, i.e. a fasting mimicking diet (FMD, Prolon®) or glycocalyx mimetic supplementation (EndocalyxTM ) could stabilize microvascular function in Surinamese South-Asian patients with type 2 diabetes (SA-T2DM) in the Netherlands, a patient population more prone to develop vascular complications. SUBJECTS/METHODS: A randomized, placebo controlled, 3-arm intervention study was conducted in 56 SA-T2DM patients between 18 and 75 years old, for 3 consecutive months, with one additional follow up measurement 3 months after the last intervention...

Formation of organo-typical vascular networks requires cross-talk between differentiating parenchymal cells and developing blood vessels. Here we identify a Vegfa driven venous sprouting process involving parenchymal to vein cross-talk regulating venous endothelial Vegfa signaling strength and subsequent formation of a specialized angiogenic cell, prefabricated with an intact lumen and pericyte coverage, termed L-Tip cell. L-Tip cell selection in the venous domain requires genetic interaction between vascular Aplnra and Kdrl in a subset of venous endothelial cells and exposure to parenchymal derived Vegfa and Apelin...

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have emerged as a novel category of blood glucose-lowering drugs in clinical recommendations for a wide range of diseases. SGLT2 inhibitors are promising anti-inflammatory agents by acting either indirectly via improving metabolism and reducing stress conditions or via direct modulation of inflammatory signaling pathways. The SGLT2 inhibitors empagliflozin and dapagliflozin better vascular function and avert vascular aging by decreasing the reactive oxygen species (ROS) content and increasing nitric oxide bioavailability, respectively...

Chronic wounds pose a significant global public health challenge due to their suboptimal treatment efficacy caused by bacterial infections and micro-circulatory disturbances. Inspired by the bio-functionality of natural skin, we bioengineered an artificial skin (HV@BC@TBG) with bacterial cellulose (BC) sandwiched between photosensitizers (PS) and functionalized living cells. Glucose-modified PS (TBG) and vascular endothelial growth factor (VEGF)-functionalized living cells (HV) were successively modified on each side of BC through biological metabolism and bio-orthogonal reaction...

VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta...

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a societal burden due to the lack of effective treatment and incomplete pathophysiology understanding. This review explores the intricate connections among liver sinusoidal endothelial cells (LSECs), platelets, neutrophil extracellular traps (NETs), and coagulation disruptions in MASLD pathogenesis. In MASLD's early stages, LSECs undergo capillarization and dysfunction due to excessive dietary macronutrients and gut-derived products...