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

Ziang Zhu,Jai Kumar,Colleen Hadigan,Marta Catalfamo,Princy Kumar,Jing Qin,Jason V Baker,Jinya Chen,Irini Sereti,Tong Li

doi:10.3389/fimmu.2021.663412

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 in vitro 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 LIN4-CD45-CD34+ and LIN4-CD45dimCD34+ in PWH. We found that the phenotype but not frequencies were associated with biomarkers of inflammation. In addition, the percentage of LIN4-CD45dimCD34+ 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.

Highlights

In people with HIV (PWH), immune activation and inflammation is associated with cardiovascular risk independently of the traditional risk factors or duration of antiretroviral treatment and CD4 counts [1,2,3,4,5,6,7,8,9,10,11,12]
Two Circulating Subsets LIN4-CD45-CD34+ and LIN4-CD45dimCD34+ of Progenitor Cells Are Detected in PBMCs From People with HIV (PWH)
From in vitro cultures of PBMCs, two progenitors have been identified, the EPC/ECFC have been defined as CD45 negative whereas, the angiogenic or colony forming unit endothelial cells (CFU-EC), which are hematopoietic origin and express CD45 [14, 15, 18, 19, 22]

Summary

INTRODUCTION

In people with HIV (PWH), immune activation and inflammation is associated with cardiovascular risk independently of the traditional risk factors or duration of antiretroviral treatment and CD4 counts [1,2,3,4,5,6,7,8,9,10,11,12]. The other subset of progenitor cells is the “angiogenic or colony forming unit endothelial cells” (CFU-EC) These cells have hematopoietic origin, and while they cannot differentiate into endothelial cells, they promote vasculogenesis by the secretion of critical growth factors [17, 22]. Recent evidence had shown that a subset of T cells can promote angiogenesis by secreting growth factors that drives proliferation and differentiation of endothelial progenitor cells Because of these properties these T cells are called angiogenic T cells (Tangs) [22, 23]. One study reported that factors present in the serum from PWH alters the functional properties of EPC/ECFC isolated from cord blood of healthy volunteers These observations propose that systemic inflammation in the setting of HIV infection can influence the functionality with no changes in their frequency [33].

Participants

RESULTS

DISCUSSION

ETHICS STATEMENT