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Exosomes from HIV-activated monocytes induce endothelial cell activation

来自 HIV 激活的单核细胞的外泌体诱导内皮细胞激活

基本信息

批准号：
8992717
负责人：
Lynn PULLIAM
金额：
$ 23万
依托单位：
NORTHERN CALIFORNIA INSTITUTE/RES/EDU
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-02 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8992717
关键词：
Acquired Immunodeficiency Syndrome Adhesions Age Arterial Fatty Streak Atherosclerosis Blood Cells Blood Circulation CCL2 gene Cardiovascular Diseases Carotid Artery Ulcerating Plaque Cell Adhesion Molecules Cell Count Cells Cholesterol Chronic Comorbidity Data Disease Endothelial Cells Endothelium Foam Cells Functional disorder Gene Expression Gene Expression Profile HIV HIV Infections HIV Seropositivity HIV-1 Human Immune Immune response Immune system Individual Infection Intercellular adhesion molecule 1 Interferon-alpha Interferons Lipids Lipopolysaccharides Low-Density Lipoproteins Messenger RNA MicroRNAs Myeloid Cell Activation Nucleic Acids Phenotype Physiological Plasma Predisposition Prevalence Proteins Recruitment Activity Reporting Risk Risk Factors Role Shapes Staining method Stains Therapeutic Tissues Vesicle Viral Viral Load result abstracting age related arterial lesion atherogenesis cardiovascular risk factor cytokine effective therapy experience immune activation in vivo interest lipid metabolism macrophage migration monocyte novel public health relevance reconstitution scavenger receptor uptake

项目摘要

DESCRIPTION (provided by applicant): HIV-infected individuals continue to have more extensive cardiovascular disease than expected for their age. While successful therapy can suppress viral load, immune reconstitution is not fully achieved. Some individuals with HIV infection continue to have an activated type 1 interferon (IFN) monocyte profile with circulating low levels of lipopolysaccharide (LPS). We reported that monocytes from HIV-infected subjects have an increase in the major scavenger receptor for lipid uptake and foam cell formation. We also showed that monocytes from HIV infection accumulated more lipids than control uninfected subjects. We hypothesize that activated monocytes from HIV-infected individuals are a risk factor different from HIV-negative subjects with atherosclerosis and carry an activated phenotype that supports modified lipid uptake. Here we show that lipid vesicles called exosomes, secreted from IFN/LPS primed monocytes, can be transferred to human endothelial cells and induce the adhesion molecules ICAM-1 and CCL2 (MCP-1). Monocytes normally secrete exosomes and can transfer miRs, mRNA, cytokines and proteins to other cells including endothelial cells. We will isolate monocyte exosomes from HIV-infected and control individuals to determine their role in endothelial cell activation. We propose to identify what factors in the exosomes induce endothelial cells to promote monocyte adhesion and migration, the initial steps for atherosclerotic plaque formation. Factors identified from monocyte exosomes may present novel targets for treatment that could decrease cardiovascular risk as well as other HIV-associated co-morbidities.