The role of PLVAP in endothelial cells

Abstract

Endothelial cells play a major part in the regulation of vascular permeability and angiogenesis. According to their duty to fit the needs of the underlying tissue, endothelial cells developed different subtypes with specific endothelial microdomains as caveolae, fenestrae and transendothelial channels which regulate nutrient exchange, leukocyte migration, and permeability. These microdomains can exhibit diaphragms that are formed by the endothelial cell-specific protein plasmalemma vesicle-associated protein (PLVAP), the only known protein component of these diaphragms. Several studies displayed an involvement of PLVAP in diseases as cancer, traumatic spinal cord injury, acute ischemic brain disease, transplant glomerulopathy, Norrie disease and diabetic retinopathy. Besides an upregulation of PLVAP expression within these diseases, pro-angiogenic or pro-inflammatory responses were observed. On the other hand, loss of PLVAP in knockout mice leads to premature mortality due to disrupted homeostasis. Generally, PLVAP is considered as a major factor influencing the permeability of endothelial cells and, finally, to be involved in the regulation of vascular permeability. Following these observations, PLVAP is debated as a novel therapeutic target with respect to the different vascular beds and tissues. In this review, we highlight the structure and functions of PLVAP in different endothelial types in health and disease.

Single-cell RNA sequencing analysis identifies one subpopulation of endothelial cells that proliferates and another that undergoes the endothelial-mesenchymal transition in regenerating pig hearts

“…The cell-cycle-specific Autoencoder (CSA) and clustering pipeline visualized five EC clusters ( Figure 1A ), each of which expressed elevated levels of the EC-specific surface markers Platelet And Endothelial Cell Adhesion Molecule 1 (PECAM1) ( Newman, 1994 ), Kinase Insert Domain Receptor (KDR) ( Terman et al, 1992 ), and vascular endothelial cadherin (CDH5) ( Wu et al, 2021 ) ( Figures 1B–D ; Supplementary Figure S1 ). Three of the clusters were enriched for expression of the vascular-EC (VEC) markers CD34 ( Fina et al, 1990 ) and Plasmalemma Vesicle Associated Protein (PLVAP) ( Denzer et al, 2023 ) ( Figures 1E, F ), while the other two expressed high levels of the lymphatic-EC (LEC) markers C-C Motif Chemokine Ligand 21 (CCL21) ( Johnson and Jackson, 2010 ), Prospero Homeobox 1 (PROX1) ( Wigle et al, 2002 ), and Lymphatic Vessel Endothelial Hyaluronan Receptor 1 (LYVE1) ( Banerji et al, 1999 ) ( Figures 1G–I ). Thus, the CSA appeared to separate the global cardiac EC population into three clusters of vascular ECs (VEC1-3) and two clusters of lymphatic ECs (LEC1-2).…”

Lethal COVID-19 Associates With RAAS-Induced Inflammation For Multiple Organ Damage Including Mediastinal Lymph Nodes

“…These genes also stratified with increasing viral load and were all significantly upregulated except CMTM4 , whose downregulation could promote T-cell exhaustion 19 , which is common in severe COVID-19 20 . Importantly, these genes play important roles throughout our narrative and some key aspects include: 1 ) SERPING1 is crucial for controlling complement pathway activation, a key event in severe tissue-damaging inflammation 10,21 ; 2 ) PLVAP , an endothelial cell-specific membrane protein required for controlling microvascular permeability and barrier function of gut endothelium 22 ; when deleted in mice triggers fluid and protein leakage into surrounding tissues and premature death 23 . 3 ) RNF213 encodes a C3HC4-type RING-finger domain that facilitates Class I MHC antigen processing and presentation and Wnt-signaling inhibition 24,25 .…”

Screening immune-related blood biomarkers for DKD-related HCC using machine learning

“…On the other hand, PLVAP was identified as a gene expressed explicitly in HCC vascular endothelial cells ( 46 ), and has been investigated as a therapeutic target in HCC ( 46 ), perhaps based on its ability to alter the immunosuppressive microenvironment ( 47 ). Indeed, during inflammation, PLVAP is required for leukocyte exudation into the site of inflammation and is essential for transcellular migration ( 48 , 49 ), and has also been described as a leukocyte transport molecule that plays a crucial role in immune surveillance and inflammation as it is redistributed in cells after pro-inflammatory stimuli ( 50 ). The conclusion can be drawn that PLVAP may provide a potential immune-related diagnostic indicator for patients with DKD-related HCC.…”