A. Salvati

The complex P2X7 receptor/inflammasome in perivascular fat tissue of heavy smokers

Smoking is a recognized cardiovascular risk factor. Perivascular visceral adipose tissue (PVAT) is a source of inflammatory molecules, thus contributing to atherosclerosis progression. The P2X7 receptor (P2X7R)‐inflammasome complex, crucial in determining IL‐1β and IL‐18 release, participates in this scenario. We evaluated whether smoking might affect the PVAT inflammatory phenotype and explored the putative role of the axis P2X7R‐inflammasome in this picture.

Angiotensin-II and rosuvastatin influence matrix remodeling in human mesangial cells via metalloproteinase modulation.

Objective Persistent inflammation and oxidative stress influence the progression of diabetic nephropathy. Metalloproteinases (MMPs) participate in extracellular matrix remodeling. Statins show favorable anti-inflammatory effects in chronic kidney disease. We evaluated the effect of rosuvastatin on inflammatory and pro-fibrotic responses due to exposure to different glucose or free fatty acid (FFA) concentrations. Methods Human mesangial cells (HMCs) grown at 5.5 (normal glucose) or 22 mmol/l (high glucose) glucose or exposed to FFA were treated with angiotensin-II in the presence or absence of rosuvastatin. We measured MMP-2, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 expression and activity, and quantified the fibrotic factors transforming growth factor-&bgr;1 (TGF-&bgr;1), fibronectin, and collagen IV. Results At normal glucose, angiotensin-II induced a dose-dependent downregulation of MMP-2; rosuvastatin reversed this effect. On the contrary, TIMP-2 and MMP-9 were upregulated by angiotensin-II and downregulated by rosuvastatin; the effects on TIMP-1 were negligible. Some of the angiotensin-II effects were potentiated in the presence of high glucose and FFA; under both conditions, rosuvastatin was able to reverse these effects. MMP-2 and MMP-9 activity followed the same trend of expression, with rosuvastatin able to upregulate MMP-2 activity. The modulation of the MMP/TIMP system was paralleled by an increase in TGF-&bgr;1, fibronectin, and collagen-IV; all were reduced by rosuvastatin treatment. Silencing the MMP-2 gene confirmed its role in modulating some of these angiotensin-II effects. Conclusion Angiotensin-II induces a pro-fibrotic response in HMCs mainly via a dysregulation of the MMP-2/TIMP-2 pattern. This effect, partially amplified in the presence of high glucose and FFA, is reversed by rosuvastatin, suggesting another potential therapeutic application for this 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor.

P2X7 receptor polymorphisms do not influence endothelial function and vascular tone in neo-diagnosed, treatment-naive essential hypertensive patients.

Objective: Endothelial dysfunction and arterial stiffness are early vascular alterations, linked to oxidative stress and inflammation, with prognostic significance in essential hypertensive patients. P2X7 receptors (P2X7R), responding to extracellular ATP, are encoded by a highly polymorphic gene and modulate inflammatory responses and cell growth, potentially playing a role in the control of vascular tone. This study evaluated the effects of P2X7R gene polymorphisms (single nucleotide polymorphisms, SNPs) on a detailed vascular hypertensive phenotype. Methods: We determined by real-time PCR two SNPs of the P2X7R gene (489C>T and 1513A>C) in 134 newly diagnosed, treatment-naive essential hypertensive patients and 131 normotensive controls (CTL). Endothelium-dependent response was assessed as flow-mediated dilatation (FMD) of the brachial artery, arterial stiffness as aortic pulse wave velocity (PWV) and augmentation index (AIx) by tonometry. Markers of oxidative stress were also measured. Results: FMD was lower (P < 0.05), whereas aortic PWV and AIx were higher (P < 0.01) in essential hypertensive patients than in CTL. The allelic distribution of the two P2X7R SNPs was similar in essential hypertensive patients and CTL, either concerning homozygosis or presence of the mutant alleles. No difference was observed for FMD, aortic PWV, AIx or markers of oxidative stress between carriers and noncarriers of the mutant alleles, either in essential hypertensive patients and in CTL. In the whole group, logistic regression showed that the mutant allele of 1513A>C was a main determinant of AIx (odds ratio 1.90; P = 0.03). Conclusion: P2X7R 489C>T and 1513A>C SNPs are not associated with altered endothelial function or arterial stiffness in untreated newly diagnosed essential hypertensive patients; a possible role in influencing peripheral wave reflection should be further addressed.

Long-term outcome of inactive and active, low viraemic HBeAg-negative-hepatitis B virus infection: Benign course towards HBsAg clearance

The difference between the long‐term outcome of low‐viraemic (HBV‐DNA≤20 000‐IU/mL, LV‐AC) and inactive HBsAg carriers (HBV‐DNA≤2000‐IU/mL, IC) remains to be defined. We studied prospectively 153 HBeAg‐negative HBsAg‐carriers with baseline HBV‐DNA≤20 000‐IU/mL and normal transaminases.

Steato-Score: Non-Invasive Quantitative Assessment of Liver Fat by Ultrasound Imaging

Non-alcoholic fatty liver disease is becoming a global epidemic. The aim of this study was to develop a system for assessing liver fat content based on ultrasound images. Magnetic resonance spectroscopy measurements were obtained in 61 patients and the controlled attenuation parameter in 54. Ultrasound images were acquired for all 115 participants and used to calculate the hepatic/renal ratio, hepatic/portal vein ratio, attenuation rate, diaphragm visualization and portal vein wall visualization. The Steato-score was obtained by combining these five parameters. Magnetic resonance spectroscopy measurements were significantly correlated with hepatic/renal ratio, hepatic/portal vein ratio, attenuation rate, diaphragm visualization and portal vein wall visualization; Steato-score was dependent on hepatic/renal ratio, attenuation rate and diaphragm visualization. Area under the receiver operating characteristic curve was equal to 0.98, with 89% sensitivity and 94% specificity. Controlled attenuation parameter values were significantly correlated with hepatic/renal ratio, attenuation rate, diaphragm visualization and Steato-score; the area under the curve was 0.79. This system could be a valid alternative as a non-invasive, simple and inexpensive assessment of intrahepatic fat.

In hepatitis C infected patients with cirrhosis squamous cell carcinoma antigen (SCCA)-IgM levels may contribute to identify the individual risk of hepatocellular carcinoma development after antiviral therapy

In hepatitis C infected patients with cirrhosis squamous cell carcinoma antigen (SCCA)-IgM levels may contribute to identify the individual risk of hepatocellular carcinoma development after antiviral therapy G. Ricco, D. Cavallone, P. Pontisso, G. Fassina, A. Gallotta, P. Colombatto, F. Oliveri, V. Romagnoli, B. Coco, A. Salvati, F. Bonino, M.R. Brunetto. Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, Pisa; Internal Medicine, University of Padua, Padua; Xeptagen S.p.a. VEGA Science Park, Marghera, Venice; UPMC Institute for Health, Chianciano Terme, Siena; Clinical and Experimental Medicine, University of Pisa, Pisa, Italy E-mail: riccogabriele@gmail.com