Endothelial Colony-Forming Cell Function Is Reduced During HIV Infection

Abstract

Background: Human immunodeficiency virus (HIV) may be related to cardiovascular disease through monocyte activation-associated endothelial dysfunction.

Methods: Blood samples from 15 HIV-negative participants (the uninfected group), 8 HIV-positive participants who were not receiving antiretroviral therapy (ART) (the infected, untreated group), and 15 HIV-positive participants who were receiving ART (the infected, treated group) underwent flow cytometry of endothelial colony-forming cells (ECFCs) and monocyte proportions. IncuCyte live cell imaging of 8 capillary proliferative capacity parameters were obtained from cord blood ECFCs treated with participant plasma.

Results: The ECFC percentage determined by flow cytometry was not different between the study groups; however, values of the majority of capillary proliferative capacity parameters (ie, cell area, network length, network branch points, number of networks, and average tube width uniformity) were significantly lower in infected, untreated participants as compared to values for uninfected participants or infected, treated participants (P < .00625 for all comparisons). CD14+CD16+ intermediate monocytes and soluble CD163 were significantly and negatively correlated with several plasma-treated, cord blood ECFC proliferative capacity parameters in the combined HIV-positive groups but not in the uninfected group.

Conclusions: Cord blood ECFC proliferative capacity was significantly impaired by plasma from infected, untreated patients, compared with plasma from uninfected participants and from infected, treated participants. Several ECFC functional parameters were adversely associated with monocyte activation in the HIV-positive groups, thereby suggesting a mechanism by which HIV-related inflammation may impair vascular reparative potential and consequently increase the risk of cardiovascular disease during HIV infection.

Keywords: ECFC; HIV-1; cardiovascular; endothelium; monocytes.

Figure 1.

Phase contrast images, with both network and skeletal masks, of representative capillary networks from individuals who were human immunodeficiency virus (HIV) negative (uninfected), HIV positive and not receiving antiretroviral therapy (ART; infected, untreated), or HIV positive and receiving ART (infected, treated), using the IncuCyte live image analysis platform. The skeletal mask is set to identify intact vascular cords with single endothelial cells lining the walls of the capillary-like structures. Cord blood endothelial colony-forming cells were treated with plasma from the study participants. The capillary network from the infected, untreated participant and, to a lesser extent, from the infected, treated participant, was appreciably reduced as compared to that from the uninfected control participant.