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Context: We have previously identified neutrophil gelatinase-associated lipocalin (NGAL) as one of the genes mediating the oncogenic activity of nuclear factor-?B in human anaplastic thyroid carcinomas (ATCs). Objectives: To further investigate the role of NGAL in thyroid cancer, we established NGAL knocked-down and NGAL overexpressing ATC cell lines. Results: We found that the ability of NGAL knocked-down cells to degrade Matrigel in a transwell invasion assay and to form lung metastasis in nude mice was decreased. Because NGAL binds matrix metalloproteinase-9 (MMP-9), to form a macromolecular complex involved in the regulation of metastatic spread of cancer cells and given the strong expression of both genes in tissue specimens from human ATCs, we analyzed the MMP-9 enzymatic activity in NGAL-null ATC cells. Enzymatic immunoassays show that MMP-9 activity is reduced in NGAL-null ATC cells, even if its expression is not affected by NGAL inhibition. Ectopic expression of NGAL in an ATC cell line not expressing NGAL determines an increase of its metastatic property. The use of a mutated form of NGAL, unable to bind MMP-9, has no positive effect on the invasive potential of ATC cells and does not improve the MMP-9 enzymatic activity. Conclusions: Our results indicate NGAL as a novel target of nuclear factor-?B prometastatic activity in thyroid cancer through enhancement of MMP-9 enzymatic activity.

Summary Background and aim Metabolic syndrome (MS) carries an increased risk for cardiovascular events and there is a growing awareness that large artery stiffening is a powerful predictor of cardiovascular morbidity and mortality. Little is known about the relationship of MS with aortic stiffness. The aim of our study was to analyze, in patients with essential hypertension, the influence of MS, defined according to the criteria proposed by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP-ATP III), on carotid–femoral pulse wave velocity (PWV), a measure of aortic stiffness. Methods Ninety-three untreated essential hypertensives, aged between 23 and 61 years, without diabetes mellitus, were studied. All subjects underwent routine blood chemistry, oral glucose tolerance test with glucose and insulin determinations, albumin excretion rate (AER) measurement, 24-h ambulatory blood pressure monitoring, and measurement of carotid–femoral PWV, by means of a computerized method. Results Patients with MS (n = 28) showed higher age-adjusted carotid–femoral PWV (10.1 ± 1.4 vs 9.3 ± 1.4 m/s; p = 0.01) when compared to subjects without MS. This difference held after controlling for gender and for 24-h mean blood pressure (MBP) (p = 0.02) and lost its statistical significance after further adjustment for AER. In a multiple regression model, excluding the individual components of MS, in which metabolic syndrome was added along with age, gender, smoking habit, LDL cholesterol, HOMA index, 24-h MBP and 24-h heart rate, MS remained independently associated with carotid-femoral PWV (β = 0.29; p = 0.002). The statistical significance of this association disappeared after the inclusion into this model of AER. Conclusions Metabolic syndrome is associated with an increased aortic stiffness. Main explanatory factors of this association are age, systolic blood pressure and albumin excretion rate.

MuleG, Nardi E, Cottone S, Cusimano P, Volpe V, Piazza G, MongioviR, Mezzatesta G, Andronico G, Cerasola G (Universitadi Palermo, Palermo, Italy). Influence of metabolic syndrome on hypertension-related target organ damage. J Intern Med 2005; 257: 503-513. Objectives. The aim of our study was to analyse, in a wide group of essential hypertensive patients without diabetes mellitus, the influence of metabolic syndrome (MS) (defined according to the criteria laid down in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults) on markers of preclinical cardiac, renal and retinal damage. Design. Cross-sectional study. Setting. Outpatient hypertension clinic. Subjects and methods. A total of 353 young and middle-aged hypertensives, free from cardiovascular and renal diseases (and 37% of whom had MS), underwent echocardiographic examination, microalbuminuria determination and non-mydriatic retinography. Results. When compared with subjects without MS, hypertensive patients with MS exhibited more elevated left ventricular (LV) mass (either normalized by body surface area or by height elevated by a power of 2.7), higher myocardial relative wall thickness, albumin excretion rate (AER) and a greater prevalence of LV hypertrophy (57.7% vs. 25.1%; P < 0.00001), of micro- albuminuria (36.2% vs. 19.3%; P ¼ 0.002) and of hypertensive retinopathy (87.7% vs. 48.4%; P < 0.00001). These results held even after correction for age, 24-h blood pressures, duration of hypertension, previous antihypertensive therapy, and gender distribution. The independent relationships between LV mass and MS, and between AER and MS, were confirmed in multivariate regression models including MS together with its individual components. Conclusions. MS may amplify hypertension-related cardiac and renal changes, over and above the potential contribution of each single component of this syndrome. As these markers of target organ damage are well-known predictors of cardiovascular events, our results may partly explain the enhanced cardiovascular risk associated with MS.

Objectives. To evaluate, in a group of nondiabetic essential hypertensive patients with normal renal function, the relationship between albumin excretion rate (AER) and carotid-femoral pulse wave velocity (PWV), as an index of aortic stiffness. Design. Cross-sectional study. Setting. Outpatient hypertension clinic. Subjects. Seventy patients with mild-to-moderate essential hypertension, aged 42 ± 8 years, never pharmacologically treated. All subjects underwent routine laboratory tests, 24-h ambulatory blood pressure (BP) monitoring, measurement of carotid-femoral PWV, by means of a computerized method, and AER. Results. Microalbuminuric patients (AER ≥ 20 μg min−1; n = 19), when compared with normoalbuminuric subjects, showed more elevated 24-h BP (136/88 ± 10/10 vs. 128/83 ± 7/6 mmHg; P