Objective We investigated the potential relationship between T-cell phenotype, inflammation, endotoxemia,

Objective We investigated the potential relationship between T-cell phenotype, inflammation, endotoxemia, and atherosclerosis evaluated by carotid intima-media thickness (IMT) in a cohort of HIV-positive patients undergoing long-term virologically suppressive combination antiretroviral therapy (cART). current CD4+, VLs and total length of time on cART. Despite comparable ratios of CD38-conveying CD8+ cells (p?=?.95), pIMT patients exhibited higher activated memory CD8+CD38+CD45R0+ cells (p?=?.038) and apoptotic CD4+CD95+ (p?=?.01) and SRT3109 CD8+CD95+ cells (p?=?.003). In comparison to nIMT patients, iIMT patients tended to have lower figures of early differentiated CD28+CD57? memory CD4+ (p?=?.048) and CD28CCD57?CD8+ cells (p?=?.006), both of which are associated with a higher proliferative potential. Despite no differences in plasma LPS levels, pIMT patients showed significantly higher circulating levels of sCD14 than did nIMT patients (p?=?.046). No differences in anti-CMV IgG was shown. Although circulating SRT3109 levels of sCD14 seemed to be associated with a risk of ATS in an unadjusted analysis, this effect was lost after adjusting for classical aerobic predictors. Findings Despite the provision of full viral suppression by cART, a hyperactivated, pro-apoptotic T-cell profile characterizes HIV-infected patients with early vascular damage, for whom the potential contribution of subclinical endotoxemia and anti-CMV immunity should be investigated further. Introduction HIV-infected patients are at an increased risk for cardiovascular events in comparison to age-matched HIV-negative controls [1], [2]. The reason for this increased risk is usually multifactorial and entails traditional risk factors, exposure to specific SELPLG antiretroviral drugs and HIV contamination itself [1] [2], [3]. The conversation between HIV contamination and cardiovascular disease has been a major concern of the HIV field since the early cART era, when large cohort studies exhibited a relationship between antiretroviral exposure and myocardial infarction [4]C[11]. Recent studies have launched the hypothesis that chronic inflammation and immune activation can contribute to the initiation and progression of atherosclerosis (ATS) in the setting of HIV contamination [12]C[15]. Recently, some authors have also suggested an association between T-cell activation/senescence and markers of subclinical carotid artery disease, even among patients on stable cART [16]. The role of inflammation and endothelial activation/disorder in the development of ATS has SRT3109 been analyzed extensively in the general populace, and several markers, such as sVCAM-1, sICAM-1 and von Willebrand factor antigen, have been shown to reliably indicate the increased activation of endothelial cells in ATS [17], [18]. Tumor necrosis factor (TNF)- has been implicated in myocardial disorder producing from acute coronary syndrome [19], and high levels of C-reactive protein (CRP) and interleukin (IL)-6 have been associated with subclinical ATS [19]C[21]. In recent years, microbial translocation (MT) has been proposed as a main mechanism behind immune hyperactivation during HIV contamination [22]C[25], and recent studies have suggested the potential involvement of MT in the pathogenesis of ATS [26], [27]. The Bruneck study in 1999 provided the first epidemiological evidence in support of a clinical association between levels of lipopolysaccharide (LPS), MT markers, and cardiovascular risk [28]. Very recently, data from the SMART study suggested that high levels of circulating sCD14, a soluble form of the LPS receptor expressed by monocytes, were associated with an increased risk of all-cause mortality, suggesting a link between stomach damage, inflammation, immune activation and CD4+ T-cell loss [14]. Long-term successfully treated HIV infected patients have been shown to present amazingly high levels of CMV-specific effector cells, comparable to that observed in the elderly [29], allowing to speculate a role of the CMV-specific inflammatory response in immunosenescence and non-AIDS morbidity and mortality. Indeed, Hsue pIMT (22 [10]C[22] IU/ml vs 22 [10]C[22] p?=?.0.86), nor comparing nIMT, iIMT and plaque (22 [10]C[22] IU/ml vs 22 [16]C[22] IU/ml vs 19 [8]C[22] IU/ml; p?=?.57). (Physique 3G). No significant association was shown between anti-CMV IgG titer, CD8+CD38+CD45R0+ (Rho?=??0.052, p?=?0.592) and CD4+/CD8+CD95+ T-cells (Rho?=?0.053, p?=?0.589; Rho?=?0.061, p?=?0.534, respectively). Oddly enough enough, when the correlation analysis was performed only in patients with pathological IMT (pIMT), a slight positive correlation was shown between anti-CMV IgG titer and pro-apoptotic CD4+CD95+ T-cells (Rho?=?0.41, p?=?0.0136). Recognition of Factors Associated with Carotid Intima-media Thickness by Univariate and Multivariate Analyses Traditional risk factors and immunological or soluble markers that displayed a p value <.01 for the Mann-Whitney U test were included in a logistic regression model to investigate the indie factors associated with increased IMT and/or plaques, as shown in Table 2a. Given the integrative nature of SRT3109 FRS and HOMA-IR that altogether include several traditional cardiovascular risk factors, for multivariate models we specifically selected not to include other risk factors that were not associated in the univariate models. Table 2 Regression models to explore impartial factors.