Brian W Wong1, Donald Wong, Honglin Luo, Bruce M McManus. 1. UBC James Hogg Research Centre, Institute for Heart + Lung Health, St Paul's Hospital, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Abstract
BACKGROUND: Vascular endothelial growth factor (VEGF)-D is a member of the VEGF family, which can induce angiogenesis and lymphangiogenesis. We have previously demonstrated a role for VEGF-A in cardiac allograft vasculopathy (CAV). Our experiments profile the expression and localization of VEGF-D in human native atherosclerosis (NA), diabetes mellitus with atherosclerosis (DM) and CAV, and we investigate its ability to induce low-density lipoprotein (LDL) permeability in human cardiac microvascular endothelial cells (HCMEC). METHODS: VEGF-D mRNA and protein expression was characterized in coronary arteries and intramyocardial arterioles in NA, DM and CAV using in situ hybridization and immunohistochemical staining. Transendothelial electrical resistance (TER) measurements and immunocytochemical staining for platelet and endothelial cell adhesion molecule-1 and zonula occludens-1 were used to assess endothelial barrier and tight junctional integrity. LDL permeability in response to treatment with VEGF-D was measured using fluorometry in confluent HCMEC. RESULTS: Image quantitation demonstrated significant increases in VEGF-D immunoreactivity in the media of coronary arteries and intramyocardial arterioles of CAV cases, and in the intima and media of coronary arteries of DM cases. Treatment with VEGF-D, in vitro, significantly increased LDL passage through HCMEC monolayers. In conjunction, treatment with VEGF-D significantly decreased TER measurements 2 hours post-treatment and induced the formation of intercellular gaps through an extracellular signal-regulated kinase 1/2 (ERK1/2)-dependent pathway. CONCLUSIONS: VEGF-D is overexpressed in the arteries of CAV and DM cases. Treatment with VEGF-D can disrupt HCMEC tight junctions, resulting in the formation of intercellular gaps, and can also significantly increase LDL permeability through confluent monolayers.
BACKGROUND:Vascular endothelial growth factor (VEGF)-D is a member of the VEGF family, which can induce angiogenesis and lymphangiogenesis. We have previously demonstrated a role for VEGF-A in cardiac allograft vasculopathy (CAV). Our experiments profile the expression and localization of VEGF-D in human native atherosclerosis (NA), diabetes mellitus with atherosclerosis (DM) and CAV, and we investigate its ability to induce low-density lipoprotein (LDL) permeability in human cardiac microvascular endothelial cells (HCMEC). METHODS:VEGF-D mRNA and protein expression was characterized in coronary arteries and intramyocardial arterioles in NA, DM and CAV using in situ hybridization and immunohistochemical staining. Transendothelial electrical resistance (TER) measurements and immunocytochemical staining for platelet and endothelial cell adhesion molecule-1 and zonula occludens-1 were used to assess endothelial barrier and tight junctional integrity. LDL permeability in response to treatment with VEGF-D was measured using fluorometry in confluent HCMEC. RESULTS: Image quantitation demonstrated significant increases in VEGF-D immunoreactivity in the media of coronary arteries and intramyocardial arterioles of CAV cases, and in the intima and media of coronary arteries of DM cases. Treatment with VEGF-D, in vitro, significantly increased LDL passage through HCMEC monolayers. In conjunction, treatment with VEGF-D significantly decreased TER measurements 2 hours post-treatment and induced the formation of intercellular gaps through an extracellular signal-regulated kinase 1/2 (ERK1/2)-dependent pathway. CONCLUSIONS:VEGF-D is overexpressed in the arteries of CAV and DM cases. Treatment with VEGF-D can disrupt HCMEC tight junctions, resulting in the formation of intercellular gaps, and can also significantly increase LDL permeability through confluent monolayers.
Authors: Dana Dlouha; Milan Blaha; Eva Rohlova; Jaroslav A Hubacek; Vera Lanska; Jakub Visek; Vladimir Blaha Journal: Genes (Basel) Date: 2021-10-12 Impact factor: 4.096
Authors: Markus Sällman Almén; Jonas Björk; Ulf Nyman; Veronica Lindström; Magnus Jonsson; Magnus Abrahamson; AnnaLotta Schiller Vestergren; Örjan Lindhe; Gary Franklin; Anders Christensson; Anders Grubb Journal: Kidney Int Rep Date: 2018-09-13