HIV vasculopathy

Abstract

Objective To determine the relationships between Krüppel-like Factors (KLF) 2 and 4, immune-activation, and sub-clinical vascular disease in HIV-infected patients on antiretroviral therapy. Design Double blind, randomized, placebo-controlled trial Methods We studied 74 HIV-infected adults on antiretroviral therapy enrolled in a randomized clinical trial of statin therapy. KLF2 and KLF4 gene expression was measured by quantitative polymerase chain reaction from peripheral blood mononuclear cells (PBMCs) at baseline and after 24 weeks of 10mg daily rosuvastatin or placebo. At the same time points, T-cell and monocyte activation were assessed by flow cytometry and vascular health was assessed by cardiac computed tomography and carotid ultrasound. Results KLF4 expression was negatively correlated with duration of antiretroviral therapy (r=−0.351, p=0.004) and positively correlated with measures of immune activation: pro-inflammatory monocytes [CD14+CD16+ (r=0.343, p=0.003)], patrolling monocytes [CD14dimCD16+ (r=0.276, p=0.017] and activated CD8+ T-lymphocytes [CD8+DR+CD38+ (r=0.264, p=0.023)]. KLF2 expression was negatively correlated with subclinical atherosclerosis: mean-mean common carotid artery intima media thickness (CIMT) (r= −0.231, p=0.048), mean-max CIMT (r= −0.271, p=0.020) and coronary artery calcium score (r=−0.254, p=0.029). There were no statistically significant changes in KLF2/4 expression in PBMCs after 24 weeks of rosuvastatin. Conclusions Expression of KLF4 in PBMCs positively correlates with cellular markers of immune activation, while KLF2 expression negatively correlates with markers of subclinical atherosclerosis in this HIV-infected population on antiretroviral therapy. Additional studies are needed to determine if targeted interventions might alter KLF2/4 expression to reduce inflammation and vascular risk in humans.

Transcriptomic analysis of monocytes from HIV-positive men on antiretroviral therapy reveals effects of tobacco smoking on interferon and stress response systems associated with depressive symptoms

“…In particular, KLF4 encodes the Krüppel-like factor 4 transcription factor induced by interferon-γ and other pro-inflammatory cytokines in a Stat1-dependent manner in human macrophages and THP-1 monocyte-derived cell lines [45]. Klf4 is involved in diverse biological processes [46], including inflammatory monocyte differentiation [47], and vascular inflammation in both HIV-infected persons and the general population [48, 49]. In this study, KLF4 was among top DE genes upregulated in HIV+ nonsmokers and further upregulated in HIV+ smokers (Fig.…”

Krüppel-like factor 4 (KLF4): What we currently know

“…KLF4 expression in PBMCs positively correlates with cellular markers of immune activation (89). KLF4 is also induced by high-density lipoproteins and can promote atherosclerosis through the upregulation of scavenger receptor class B type 1 in PBMCs and human THP-1 monocytes (90).…”