PB1291 - Biomarkers of endothelial cell dysfunction in HIV-infected patients

Background: HIV-infected patients are at increased risk of vascular disease and arterial thrombosis, linked to endothelial dysfunction and chronic inflammation.

Aims: To evaluate the presence of biomarkers of endothelial dysfunction in plasma the coagulation status of leukocytes in HIV-infected patients.

Methods: Venous blood was collected with approval from the Wits Human Research Ethics Committee from healthy controls (n=13) and compared with samples collected from HIV-infected patients (n=22). Biomarker levels in plasma were evaluated using the MILLIPLEX MAP Human Cardiovascular Disease (CVD) Magnetic Bead Panel 2 (Merck KGaA, Darmstadt, Germany). Flow cytometry was performed on an LSR II flow cytometer and analysed on FlowJo (both Becton-Dickinson, Franklin Lakes, USA). Monocytes and neutrophils were identified by light scatter characteristics and expression of HLA-DR, CD33, CD14, CD16 and CD69 (monocytes) and CD33, CD16 and CD69 (neutrophils). Tissue factor was expressed as a percentage of positive cells. Descriptive statistics were computed and values were compared with a Mann-Whitney U test on Graphpad Prism (Graphpad, California, United States). A p-value of < 0.05 was considered significant.

Results: HIV-infected patients showed elevated humoral markers of inflammation and endothelial dysfunction (GDF-15, p-selectin and sICAM-1) when compared with uninfected controls. The leukocytes in these patients showed upregulation of the procoagulant tissue factor expression (Table 1).

Conclusion(s): HIV infection predisposes to endothelial dysfunction. In this study, we investigated the contribution of both humoral and cellular factors to increased cardiovascular risk. GDF-15, an independent biomarker of cardiovascular disease and sICAM-1 and p-selectin, markers associated with leukocyte trafficking across the endothelium were significantly elevated in HIV-infected patients in the absence of clinical cardiovascular disease. Tissue factor expression by leukocytes was also increased and which contributed to a general procoagulant state. Future directions will examine these factors in HIV-infected patients with established vascular disease.