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慢性 HIV 感染中炎症和免疫激活对循环内皮祖细胞的作用。

The Role of Inflammation and Immune Activation on Circulating Endothelial Progenitor Cells in Chronic HIV Infection.

机构信息

Department of Microbiology and Immunology. Georgetown University School of Medicine, Washington, DC, United States.

Division of Infectious Diseases and Tropical Medicine, Georgetown University School of Medicine, Washington, DC, United States.

出版信息

Front Immunol. 2021 May 17;12:663412. doi: 10.3389/fimmu.2021.663412. eCollection 2021.

Abstract

Endothelial inflammation and damage are the main drivers of cardiovascular risk/disease. Endothelial repair is mediated in part by recruitment of bone marrow endothelial progenitor/endothelial colony forming cells (EPC/ECFC). People with HIV (PWH) have increased cardiovascular risk and the impact of infection in endothelial repair is not well defined. The low frequencies and challenges to isolation and differentiation of EPC/ECFC from PBMCs had made it difficult to study their role in this context. We hypothesized that HIV driven inflammation induces phenotypic changes that reflects the impact of infection. To test this hypothesis, we evaluated expression of markers of trafficking, endothelial differentiation, and angiogenesis, and study their association with biomarkers of inflammation in a cohort of PWH. In addition, we investigated the relationship of circulating endothelial progenitors and angiogenic T cells, a T cell subset with angiogenic function. Using a flow cytometry approach, we identified two subsets of circulating progenitors LIN4CD45CD34 and LIN4CD45CD34 in PWH. We found that the phenotype but not frequencies were associated with biomarkers of inflammation. In addition, the percentage of LIN4CD45CD34 was associated with serum levels of lipids. This data may provide a new tool to better address the impact of HIV infection in endothelial inflammation and repair.

摘要

内皮炎症和损伤是心血管风险/疾病的主要驱动因素。内皮修复部分由骨髓内皮祖细胞/内皮集落形成细胞 (EPC/ECFC) 的募集介导。艾滋病毒感染者 (PWH) 心血管风险增加,感染对内皮修复的影响尚不清楚。从 PBMC 中分离和分化 EPC/ECFC 的频率低且具有挑战性,这使得很难在这种情况下研究它们的作用。我们假设 HIV 驱动的炎症诱导表型变化,反映了感染的影响。为了验证这一假设,我们评估了 PWH 队列中迁移、内皮分化和血管生成标志物的表达,并研究了它们与炎症生物标志物的关系。此外,我们研究了循环内皮祖细胞和血管生成 T 细胞(具有血管生成功能的 T 细胞亚群)的关系。使用流式细胞术方法,我们在 PWH 中鉴定出两种循环祖细胞亚群 LIN4CD45CD34 和 LIN4CD45CD34。我们发现表型而非频率与炎症生物标志物相关。此外,LIN4CD45CD34 的百分比与血清脂质水平相关。该数据可能为更好地解决 HIV 感染对内皮炎症和修复的影响提供了新工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f22/8165313/380ae66c155a/fimmu-12-663412-g001.jpg

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