Intima modifier locus 2 controls endothelial cell activation and vascular permeability
| Autor: | Bradford C. Berk, Tamlyn N. Thomas, Chenjing Wang, Elaine M. Smolock, Martha L. Zettel, Xing Qiu, Vyacheslav A. Korshunov, Sri N. Batchu, Keigi Fujiwara, Ryan M. Burke |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Physiology Vascular Cell Adhesion Molecule-1 Locus (genetics) Inflammation Vascular permeability chemical and pharmacologic phenomena Biology Polymorphism Single Nucleotide Cell size Capillary Permeability Mice Congenic Immune system Internal medicine Genetics medicine Animals Significant risk Molecular Genetics of Complex Traits Cell Size Genome Sequence Analysis RNA Endothelial Cells Tunica intima Endothelial stem cell medicine.anatomical_structure Endocrinology Gene Ontology Genetic Loci Immunology Endothelium Vascular medicine.symptom Tunica Intima |
| Zdroj: | Physiological genomics. 46(17) |
| ISSN: | 1531-2267 |
| Popis: | Carotid intima formation is a significant risk factor for cardiovascular disease. C3H/FeJ (C3H/F) and SJL/J (SJL) inbred mouse strains differ in susceptibility to immune and vascular traits. Using a congenic approach we demonstrated that the Intima modifier 2 ( Im2) locus on chromosome 11 regulates leukocyte infiltration. We sought to determine whether inflammation was due to changes in circulating immune cells or activation of vascular wall cells in genetically pure Im2 (C3H/F.SJL.11.1) mice. Complete blood counts showed no differences in circulating monocytes between C3H/F and C3H/F.SJL.11.1 compared with SJL mice. Aortic vascular cell adhesion molecule-1 (VCAM-1) total protein levels were dramatically increased in SJL and C3H/F.SJL.11.1 compared with C3H/F mice. Immunostaining of aortic endothelial cells (EC) showed a significant increase in VCAM-1 expression in SJL and C3H/F.SJL.11.1 compared with C3H/F under steady flow conditions. Immunostaining of EC membranes revealed a significant decrease in EC size in SJL and C3H/F.SJL.11.1 vs. C3H/F in regions of disturbed flow. Vascular permeability was significantly higher in C3H/F.SJL.11.1 compared with C3H/F. Our results indicate that Im2 regulation of leukocyte infiltration is mediated by EC inflammation and permeability. RNA sequencing and pathway analyses comparing genes in the Im2 locus to C3H/F provide insight into candidate genes that regulate vascular wall inflammation and permeability highlighting important genetic mechanisms that control vascular intima in response to injury. |
| Databáze: | OpenAIRE |
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