ABSTRACT
BACKGROUND: Macrophage-derived foam cell formation is a hallmark of atherosclerosis and is retained during plaque formation. Strategies to inhibit the accumulation of these cells hold promise as viable options for treating atherosclerosis. Plexin D1 (PLXND1), a member of the Plexin family, has elevated expression in atherosclerotic plaques and correlates with cell migration; however, its role in macrophages remains unclear. We hypothesize that the guidance receptor PLXND1 negatively regulating macrophage mobility to promote the progression of atherosclerosis. METHODS: We utilized a mouse model of atherosclerosis based on a high-fat diet and an ox-LDL- induced foam cell model to assess PLXND1 levels and their impact on cell migration. Through western blotting, Transwell assays, and immunofluorescence staining, we explored the potential mechanism by which PLXND1 mediates foam cell motility in atherosclerosis. RESULTS: Our study identifies a critical role for PLXND1 in atherosclerosis plaques and in a low-migration capacity foam cell model induced by ox-LDL. In the aortic sinus plaques of ApoE-/- mice, immunofluorescence staining revealed significant upregulation of PLXND1 and Sema3E, with colocalization in macrophages. In macrophages treated with ox-LDL, increased expression of PLXND1 led to reduced pseudopodia formation and decreased migratory capacity. PLXND1 is involved in regulating macrophage migration by modulating the phosphorylation levels of FAK/Paxillin and downstream CDC42/PAK. Additionally, FAK inhibitors counteract the ox-LDL-induced migration suppression by modulating the phosphorylation states of FAK, Paxillin and their downstream effectors CDC42 and PAK. CONCLUSION: Our findings indicate that PLXND1 plays a role in regulating macrophage migration by modulating the phosphorylation levels of FAK/Paxillin and downstream CDC42/PAK to promoting atherosclerosis.
Subject(s)
Atherosclerosis , Cell Movement , Foam Cells , Mice, Inbred C57BL , Paxillin , Animals , Paxillin/metabolism , Foam Cells/metabolism , Foam Cells/pathology , Mice , Atherosclerosis/metabolism , Atherosclerosis/pathology , Signal Transduction , Lipoproteins, LDL/metabolism , Male , Nerve Tissue Proteins/metabolism , Nerve Tissue Proteins/genetics , cdc42 GTP-Binding Protein/metabolism , Macrophages/metabolism , Focal Adhesion Kinase 1/metabolism , Focal Adhesion Kinase 1/genetics , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Plaque, Atherosclerotic/metabolism , Plaque, Atherosclerotic/pathology , Disease Models, Animal , Receptors, Cell Surface/metabolism , Receptors, Cell Surface/genetics , Mice, Knockout , Membrane Glycoproteins , Intracellular Signaling Peptides and ProteinsABSTRACT
Temperature step change is the typical transient thermal environment. The purpose of this study was to explore the association of subjective and objective parameters in a step-change environment, including thermal sensation vote (TSV), thermal comfort vote (TCV), mean skin temperature (MST) and endogenous dopamine (DA). Three temperature step changes defined as I3 (15 °C-18 °C to 15 °C), I9 (15 °C-24 °C to 15 °C) and I15 (15 °C-30 °C to 15 °C) were designed for this experiment. Eight male and eight female healthy subjects who participated in the experiment reported thermal perception (TSV and TCV). Skin temperatures of six body parts and DA were measured. Results show that the inverted U-shaped in TSV and TCV was deviated by seasonal factors of the experiment. The deviation direction of TSV in winter was to the warm sensation side, which was opposite to the inherent cold and hot impression of people in winter and summer. The association between dimensionless dopamine (DA*), TSV and MST were described as follows: DA* was the U-shaped change with exposure times when MST was not greater than 31 °C, and TSV was at -2 and -1, and DA* increased with exposure times when MST was greater than 31 °C, and TSV was at 0, 1 and 2. The changes in the body heat storage and autonomous thermal regulation under temperature step changes may potentially be related to the concentration of DA. The human state on thermal nonequilibrium and stronger thermal regulation would correspond to a higher concentration of DA. This work is conducive to exploring the human regulation mechanism in a transient environment.
Subject(s)
Dopamine , Skin Temperature , Humans , Male , Female , Seasons , Cold Temperature , Hot Temperature , Thermosensing/physiology , TemperatureABSTRACT
Community-based home hospice care provided by community service centers and family physician teams aims to alleviate the suffering of terminally ill patients and help them to receive end-of-life care and pass away at home.The Puhuangyu Community Health Service Center established the home hospice care model of PUMCH-Puhuangyu Coordination at the end of 2019.The model has been practiced and improved to date.This paper introduces this model of home hospice care.
Subject(s)
Home Care Services , Hospice Care , Hospices , Terminal Care , Humans , Tertiary Care CentersABSTRACT
Objective To investigate the feasibility of home hospice care based on the practical experience in Puhuangyu community of Beijing.Methods We selected the patients assessed by hospice care team and receiving home hospice care from Puhuangyu Community Health Service Center of Beijing from January 1,2020 to December 31,2021.The clinical manifestations,hospice services received,and place of death of the patients were analyzed. Results A total of 24 patients were included in this study.They mainly suffered from malignant tumors(18 patients,75.0%),with pain as the most common symptom(12 patients,50.0%).The patients received a variety of hospice services through a combination of outpatient visits,home visits,and WeChat follow-up.The service time of each patient was(2.8±1.7) h each week on average and 57.9%(11/19) of the patients passed away at home. Conclusions The home hospice care in Puhuangyu community has a stable source of patients.The members of this hospice team can provide a variety of home hospice services.With this model,the wish to pass away at home can be achievable for most patients.Therefore,this model of community-based home hospice care is feasible.
