Platelet-Activating Factor and Its Basic Metabolic Enzymes in Blood of Naive HIV-Infected Patients

Abstract

Platelet-activating factor (PAF), a mediator of proatherosclerotic inflammatory processes, is also implicated in endothelial dysfunction during human immunodeficiency virus (HIV) infection. We examined PAF metabolism in blood of naive male patients, 8 with early HIV infection (group A) and 17 just before treatment initiation (group B), versus 18 healthy age-matched males (group C). Statistical analysis was performed with 1-way analysis of variance (ANOVA) criterion and Pearson r test. Higher PAF biosynthesis in patients' leukocytes versus group C was accompanied by an increase in lipoprotein-associated phospholipase A2 (Lp-PLA2) activity that degrades PAF. Moreover, PAF synthesis was higher and Lp-PLA2 activity was lower in group B compared to group A. Lipoprotein-associated phospholipase A2 was positively correlated with viral load and negatively correlated with CD4 cell counts in group B. The activities of PAF-basic biosynthetic enzymes in patients' leukocytes were also negatively correlated with CD4 cell counts. The observed continuous increase in PAF biosynthesis during HIV infection progress seems to amplify the risk of AIDS manifestations and/or cardiovascular complications in HIV-infected patients, while a subsequent increase in Lp-PLA2 activity seems to be a host response.

Effects of Highly Active Antiretroviral Therapy on Platelet Activating Factor Metabolism in Naïve HIV-Infected Patients: II) Study of the Abacavir/Lamivudine/Efavirenz Haart Regimen

“…This is in accordance with the study of Klovidhunic et al reporting that suppression of IlIV viremia by either a protease inhibitor or lamivudine was not accompanied by a lower level of LpPLA 2 activity (30). In the present study we found that LpPL~activity was positively correlated with viral load at baseline, an observation that is consistent with our previous reports (9). However, it should also be mentioned that the positive correlation of LpPLA 2 with viral load was diminished in partial correlations after adjusting for several cofounders such as LDL cholesterol which is known to be the main carrier of this enzyme in plasma.…”

“…Therefore, since PAF downregulates CD4 proliferation (29), it is possible that the negative correlation of Lyso-PAF-AT with CD4 cell counts at baseline reflects an implication of increased PAF levels in HIVinduced immunosuppression. This observation is in accordance with our previous data reporting a negative correlation between Lyso-PAF-AT of HLs and CD4 cell counts (9). However, naive patients differed between our two studies in terms of duration of HIV infection and viral load levels (9).…”

“…With this point ofview, we have previously described that PAP biosynthesis is induced in patients with early HIV infection compared to control subjects, an induction that was more profound in HIV-infected patients with higher viral load levels just before HAART initiation (9).…”

“…However, its basic enzyme, PAF-CPT, seems to be implicated in systemic inflammatory manifestations such as cancer (7), central nervous system failure (8) and AIDS (9). On the other hand, although it is well established that the remodeling pathway is activated mainly during acute inflammatory disorders, it has also been found to be activated in systemic ones (7,9,10). Its main enzyme lyso-PAF-AT under resting conditions contributes to membrane glycerophospholipids production and membrane biogenesis, while upon acute inflammatory stimulation leads to PAF production (10).…”

Paf-Metabolic Enzymes and Paf-like Activity inL. InfantumandL. MajorPromastigotes

“…In mammals for example, the de novo pathway contributes to PAF synthesis for maintaining its basal levels under physiological conditions, while the remodeling pathway is activated under inflammatory situations. However, the de novo pathway, especially PAF-CPT, may contribute to systemic disorders such as cancer (25), central nervous system failure (26), and AIDS (27). As far as we know there has been no previous study to give sufficient data regarding the contribution of these two distinct basic PAF biosynthetic enzymes in any protozoa.…”