Endothelial activation biomarkers increase after HIV-1 acquisition

Abstract

Objective We aimed to determine whether endothelial activation biomarkers increase after HIV-1 acquisition, and whether biomarker levels measured in chronic infection would predict disease progression and death in HIV-1 seroconverters. Design HIV-1-seronegative Kenyan women were monitored monthly for seroconversion, and followed prospectively after HIV-1 acquisition. Methods Plasma levels of angiopoietins-1 and -2 (ANG-1, ANG-2) and soluble vascular cell adhesion marker-1 (VCAM-1), intercellular adhesion marker-1 (ICAM-1), and E-selectin were tested in stored samples from before infection, acute infection, and at two points during chronic infection. We used non-parametric tests to compare biomarkers before and after HIV-1 acquisition, and Cox proportional-hazards regression to analyze associations with disease progression (CD4 <200 cells/μL, Stage IV disease, or ART initiation) or death. Results Soluble ICAM-1 and VCAM-1 were elevated relative to baseline in all post-infection periods assessed (p<0.0001). Soluble E-selectin and the ANG-2:ANG-1 ratio increased in acute infection (p=0.0001), and ANG-1 decreased in chronic infection (p=0.0004). Among 228 subjects followed over 1,028 person-years, 115 experienced disease progression or death. Plasma VCAM-1 levels measured during chronic infection were independently associated with time to HIV progression or death (aHR 5.36, 95% confidence interval 1.99–14.44 per log10 increase), after adjustment for set point plasma viral load, age at infection, and soluble ICAM-1 levels. Conclusions HIV-1 acquisition was associated with endothelial activation, with sustained elevations of soluble ICAM-1 and VCAM-1 post-infection. Soluble VCAM-1 may be an informative biomarker for predicting the risk of HIV-1 disease progression, morbidity, and mortality.

Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons

“…Endothelial dysfunction is a complication of acute and chronic HIV[35, 36], and markers of endothelial activation (including cellular adhesion molecules, methylarginines, fibrinogen, and D-dimer) have been associated with cardiovascular disease in HIV[34, 37, 39, 40]. Endothelial damage markers have also been associated with COPD in the general population[42–46].…”

Altered angiogenesis as a common mechanism underlying preterm birth, small for gestational age, and stillbirth in women living with HIV

“…Other studies examining angiogenic factors in nonpregnant individuals infected with HIV have shown increases in the Ang-2:Ang-1 ratio associated with acute HIV infection, and decreased Ang-1 in chronic disease. 54 In HIV-infected Kenyan women with advanced infection, Ang-2 levels decreased and Ang-1 levels increased following the initiation of ART. 55 On a cellular level, HIV-infected cells release transactivator of transcription, which accumulates on and is taken up by endothelial cells where it acts in synergy with VEGF-A to modify the cytoskeletal structure of endothelium.…”

Endothelial activation and cardiometabolic profiles of treated and never-treated HIV infected Africans

“…These adhesion molecules play an essential role in the development of vascular inflammation and endothelial dysfunction [17] which are associated with the pathogenesis of CVD [18]. Although the HIV tat protein induces ICAM and VCAM secretion [19,20], ART regimens suppress both viral load and HIV-induced vascular inflammation, leading to an improvement of endothelial activation and dysfunction [10,21].…”

“…The relationship between inflammatory pathways and the pathogenesis of HIV, especially the pathogenesis of HIV-related endothelial activation, is not well understood [21]. The interplay between factors associated with CVD and HIV, and the added influence of ART on this relationship is complex and their overall contribution to the vascular system needs further investigation.…”