Relationship between regulatory T cells subsets and lipid profile in dyslipidemic patients: a longitudinal study during atorvastatin treatment.

BACKGROUND: The CD4+ T-lymphocytes and their subtype CD4 + CD25(high)FoxP3+ regulatory T cells are receiving growing interest as major regulators of atherogenesis. We sought to investigate 1) whether the CD4 + cell subsets were expressed differently in dyslipidemic patients (Pts) and healthy subjects (HS) and 2) whether atorvastatin treatment could be associated in-vivo and in-vitro with cell changes in expression and functional response. METHODS: CD4+ subsets frequency (CD4 + CD25(high)FoxP3+, CD4 + CD25-FoxP3+) and mRNA expression for FoxP3, IL-10 and TGF-ß were evaluated in 30 consecutive Pts at baseline and after a 3-month atorvastatin therapy, and in 17 HS. RESULTS: The % of CD4 + cells did not differ between HS and Pts. The % of CD4 + CD25(high)FoxP3+ was higher in Pts than HS and did not change during treatment. The CD4 + CD25-FoxP3+ cells were similar between the two groups and were lower in Pts at visit 2. Cytokine expression and FoxP3 did not differ in HS and Pts and no substantial change was observed during treatment. At visit 1, CD4 + CD25(high)FoxP3+ cells were significantly correlated with both total-cholesterol (r = 0.570, P = 0.0002), LDL-cholesterol (r = 0.715, P = 0.0001), Apolipoprotein B (r = 0.590, P = 0.0001). In-vitro atorvastatin (up to 5 µM) failed to induce any significant modulation of cell functions. CONCLUSION: CD4 + CD25(high)FoxP3+ regulatory cells seem to be over-stimulated in the early pre-clinical phase of atherosclerosis and a relationship exists between their frequency and circulating lipids. A potential immuno-modulation by statin treatment is not achieved through a normalization in peripheral CD4 + cell subsets.

Simvastatin down-regulates the production of interleukin-8 by neutrophil leukocytes from dyslipidemic patients.

BACKGROUND: Neutrophil (PMN) leukocytes participate to the initial phases of atherosclerosis through the release of Interleukin 8 (CxCL8; IL-8) that contribute to amplification of inflammation. Aim of the study is to investigate the production of IL-8 by PMN leukocytes from dyslipidemic patients treated with simvastatin. METHODS: In 15 dyslipidemic subjects with moderately increased cardiovascular risk, assessed by Framingham Risk Score, blood samples were obtain to investigate PMNs IL-8 production [at baseline and after N-formyl-Met-Leu-Phe (fMLP) stimulation] before and after long-term (1-year) simvastatin treatment. RESULTS: The resting release of IL-8 was higher in dyslipidemic patients at baseline when compared with control subjects (p < 0.05). One year of treatment was significantly associated with reduced IL-8 production (p < 0.01). Moreover, the fMLP-induced IL-8 production in dyslipidemic untreated patients was higher than that of controls (p < 0.05) and was reduced after simvastatin treatment (p < 0.01). IL-8 release after 1 year of treatment was reduced to levels which were lower than those observed in control subjects both for resting and stimulated cytokine production (p < 0.01). CONCLUSIONS: Prolonged treatment with simvastatin is associated with a reduction of IL-8 production, suggesting the possibility of statin to modulate the pro-inflammatory response in PMNs of patients with moderately increased cardiovascular risk.

Right ventricular remodelling in mild hypertensive patients: role of left ventricular morpho-functional parameters.

Previous studies suggested that hypertensive patients with left ventricular (LV) hypertrophy display right ventricular (RV) remodelling. Few data are available about RV remodelling in naive hypertensives without severe cardiac organ damage. Our aim was to evaluate the relationship between RV and LV morpho-functional parameters in never-treated patients with grade 1 hypertension and whether central blood pressure (CBP), inflammatory and metabolic parameters are potentially associated with RV remodelling. 150 never-treated subjects without evidence of diabetes or other cardiovascular diseases were enrolled in our study. We recruited 100 patients with mild hypertension (twenty-four hours blood pressure (24 h BP) ≥ 130/80 mmHg) and 50 normotensive subjects matched for gender, age and body mass index. To estimate the LV/RV parameters, we performed echography as well as arterial tonometry to assess pulse wave analysis/velocity (PWA/PWV). We found 24 h BP, CBP and PWV were higher in hypertensive patients than in normotensives. In addition, LV mass index was higher in hypertensives, and greater RV free wall thickness was observed (5.3 ± 1.4 vs 4.6 ± 1.2 mm, P = 0.02). RV thickness correlated with interventricular septum (IVS), systolic CBP and RV E' (r = 0.50, P = 0.0001, r = 0.30, P = 0.003, r = -0.24, P = 0.015); linear regression analysis showed a correlation with only IVS (ß = 0.39, P = 0.001). RV E' was correlated with IVS, LV E' and systolic CBP (r = -0.35, P = 0.0001, r = 0.25, P = 0.012, r = -0.24, P = 0.019); the correlation with IVS and LV E' (ß = -0.310, P = 0.001; ß = 0.27, P = 0.004) was confirmed by linear regression analysis. Our study shows RV remodelling is mostly correlated with IVS thickness, supporting the ventricular interdependence hypothesis.