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author:("dozi, Elena")
1.  Hypertension in adult Fabry’s disease: is cardiotrophin-1 a diagnostic biomarker? 
Immunity & Ageing : I & A  2014;11(1):27.
Cardiotrophin-1 (CT-1), a cytokine produced by cardiomyocytes and non-cardiomyocytes in conditions of stress, can be used as a biomarker of left ventricular hypertrophy and dysfunction in hypertensive patients. Hypertension is one of the main adverse events in the third and last phase of Fabry’s disease (FD). We measured CT-1 in order to examine its correlation with the vascular and cardiac alterations at different ages and assess its potential for use as a biomarker of hypertension in FD.
The level of CT-1 was clearly higher in hypertensive adults than in adult FD patients. FD patients show a small, non-significant decrease in plasma CT-1 with age, while in hypertensive patients CT-1 in plasma rises strongly and highly significantly with age.
CT-1 can be considered a good biomarker of the progression of hypertension with age, but particular care is needed when following hypertension in FD patients, since CT-1 does not correlate the same way with this disease.
PMCID: PMC4296686  PMID: 25598833
Fabry disease (FD); Hypertension; Cardiotrophin-1 (CT-1)
2.  Interleukin-15 and Soluble Interleukin-15 Receptor α in Coronary Artery Disease Patients: Association with Epicardial Fat and Indices of Adipose Tissue Distribution 
PLoS ONE  2014;9(3):e90960.
Interleukin-15 (IL-15) is a pro-inflammatory cytokine which signals via a specific alpha receptor subunit (IL-15Rα). Increased IL-15 level has been observed in cardiovascular patients and IL-15 immunoreactivity has been detected at vulnerable atherosclerotic plaques. Due to the association between adipose tissue distribution, inflammation and coronary artery disease (CAD), we quantified IL-15 and IL-15Rα in CAD patients with different adiposity and adipose tissue distribution and we evaluated whether epicardial adipose tissue (EAT), a visceral fat depot surrounding and infiltrating myocardium, may be a source of both molecules. IL-15 and IL-15Rα proteins were quantified by enzyme-linked immunosorbent assays. Gene expression of IL-15 and IL-15Rα in EAT depots was evaluated by one colour microarray platform. EAT thickness was measured by echocardiography. Plasmatic IL-15 and IL-15Rα levels were higher in CAD than non-CAD patients. After classification according to adipose tissue distribution, IL-15 was higher in CAD patients with increased abdominal adiposity. Increased level of IL-15Rα was observed both in CAD and non-CAD patients with increased abdominal fat. EAT was a source of IL-15 and IL-15Rα and their expression was higher in CAD patients with increased EAT thickness. In conclusion, our data suggest that circulating levels of IL-15 and IL-15Rα seem to reflect visceral distribution of adipose tissue and that EAT may be a potential source of both IL-15 and IL-15Rα. Future studies on the relationship between IL-15, visceral fat and characteristics of atherosclerotic plaques could help to better understand the complex biology of this cytokine.
PMCID: PMC3948349  PMID: 24603895
3.  Low heart-type fatty acid binding protein level during aging may protect down syndrome people against atherosclerosis 
Aging is considered an important independent risk factor for atherosclerosis. Down syndrome people (DS) display an accelerated aging process compared to healthy subjects, anyway they are relatively resistant to developing atherosclerosis. The mechanisms involved in such protective effect are not well known. Since heart-type fatty acid binding protein (H-FABP) is a protein involved in the transport of fatty acids and it has been recently correlated with the presence of atherosclerosis, we aimed to measure H-FABP level both in DS and in healthy subjects during aging to evaluate the association between this molecule, aging and atherosclerosis.
We quantified plasmatic H-FABP level in three groups of male DS and age-matched healthy subjects (children, age 2–14 years; adults, age 20–50 years; elderly, > 60 years) using a biochip array analyzer. We observed that aging is associated with increased H-FABP level in healthy subjects but not in DS which display both the same protein level in the different ages of life and have also lower level compared to their age-matched healthy subjects.
Reduced H-FABP level during aging in DS may play a protective role against atherosclerosis. The potential involvement of H-FABP in the relationship between aging, atherosclerosis and development of coronary artery disease needs further investigations.
PMCID: PMC3575247  PMID: 23339583
Aging; Atherosclerosis; Down syndrome; Heart-type fatty acid binding protein
4.  Natural zeolites chabazite/phillipsite/analcime increase blood levels of antioxidant enzymes 
Imbalance between reactive oxygen species generation and antioxidant capacity induces a condition known as oxidative stress which is implicated in numerous pathological processes. In this study we evaluated whether natural zeolites chabazite/phillipsite/analcime may affect the levels of different antioxidant enzymes (gluthatione peroxidase, superoxide dismutase, gluthatione reductase), total antioxidant status and oxidative stress in 25 clinically healthy men, both non-smokers and smokers. Measurements were performed on whole blood or on plasma samples before (T0) and after 4-weeks zeolites intake (T1). At T1, gluthatione peroxidase, superoxide dismutase and gluthatione reductase increased compared to T0 levels, both considering all subjects as joint and after subdivision in non-smokers and smokers. Differently, a reduction in total antioxidant status was observed at T1. Anyway, total antioxidant status resulted higher than the reference values in both groups at each time point. A decrease in lipid peroxidation, a major indicator of oxidative stress assessed by monitoring thiobarbituric acid reactive substances, was also observed in all subjects at T1. Our results suggested that chabazite/phillipsite/analcime may help to counteract oxidative stress in apparently healthy subjects exposed to different oxidative stress risk factors, such as smoking, thus representing a particular kind of food with potential antioxidant properties.
PMCID: PMC3334371  PMID: 22573920
gluthatione reductase; gluthatione peroxidase; superoxide dismutase; total antioxidant status; zeolites
5.  Adipokines and Sexual Hormones Associated with the Components of the Metabolic Syndrome in Pharmacologically Untreated Subjects: Data from the Brisighella Heart Study 
We evaluated the association of the sex hormone pattern and the serum level of the main adipokines to metabolic syndrome (MS) and its components in 199 pharmacologically untreated subjects. Men and women included in the age-class subgroups were matched for body mass index, waist circumference, blood pressure, heart rate, fasting plasma glucose, and plasma lipids. Men without MS had significantly lower leptin/adiponectin ratio than men with MS. Women without MS had lower leptin and leptin/adiponectin ratio than women with MS but had significantly higher adiponectin, estrone, and dehydroepiandrosterone levels. In men, the leptin/adiponectin ratio is the main factor associated to MS diagnosis (OR: 3.36, 95% CI 1.40–8.08), while in women adiponectin alone appears to be a protective factor (OR: 0.87, 95% CI 0.79–0.95). In conclusion, in a sample of pharmacologically untreated subjects, leptin/adiponectin ratio seems to be the factor more strongly associated to MS and its components.
PMCID: PMC3216320  PMID: 22114592
6.  VEGF signalling controls GnRH neuron survival via NRP1 independently of KDR and blood vessels 
Development (Cambridge, England)  2011;138(17):3723-3733.
Gonadotropin-releasing hormone (GnRH) neurons are neuroendocrine cells that are born in the nasal placode during embryonic development and migrate through the nose and forebrain to the hypothalamus, where they regulate reproduction. Many molecular pathways that guide their migration have been identified, but little is known about the factors that control the survival of the migrating GnRH neurons as they negotiate different environments. We previously reported that the class 3 semaphorin SEMA3A signals through its neuropilin receptors, NRP1 and NRP2, to organise the axons that guide migrating GnRH neurons from their birthplace into the brain. By combining analysis of genetically altered mice with in vitro models, we show here that the alternative neuropilin ligand VEGF164 promotes the survival of migrating GnRH neurons by co-activating the ERK and AKT signalling pathways through NRP1. We also demonstrate that survival signalling relies on neuronal, but not endothelial, NRP1 expression and that it occurs independently of KDR, the main VEGF receptor in blood vessels. Therefore, VEGF164 provides survival signals directly to developing GnRH neurons, independently of its role in blood vessels. Finally, we show that the VEGF164-mediated neuronal survival and SEMA3A-mediated axon guidance cooperate to ensure that migrating GnRH neurons reach the brain. Thus, the loss of both neuropilin ligands leads to an almost complete failure to establish the GnRH neuron system.
PMCID: PMC3152927  PMID: 21828096
GnRH neuron; Neuronal survival; VEGF; KDR; VEGFR2; FLK1; Neuropilin; Mouse
7.  Impaired Expression of Insulin-Like Growth Factor-1 System in Skeletal Muscle of Amyotrophic Lateral Sclerosis Patients 
Muscle & Nerve  2012;45(2):200-208.
Adult muscle fibers are a source of growth factors, including insulin-like growth factor-1 (IGF-1). These factors influence neuronal survival, axonal growth, and maintenance of synaptic connections.
We investigated the components of the IGF system in skeletal muscle samples obtained from 17 sporadic amyotrophic lateral sclerosis patients (sALS) and 29 control subjects (17 with normal muscle and 12 with denervated muscle unrelated to ALS).
The muscle expression of IGF-1 and IGF-binding proteins 3, 4, and 5 (IGF-BP3, -4, and -5, respectively), assessed by immunohistochemistry, was differently decreased in sALS compared with both control groups; conversely, IGF-1 receptor β subunit (IGF-1Rβ) was significantly increased. Western blot analysis confirmed the severe reduction of IGF-1, IGF-BP3, and -BP5 with the increment of IGF-1Rβ in sALS.
In this study we describe the abnormal expression of the IGF-1 system in skeletal muscle of sALS patients that could participate in motor neuron degeneration and should be taken into account when developing treatments with IGF-1. Muscle Nerve, 2012
PMCID: PMC3306791  PMID: 22246875
amyotrophic lateral sclerosis; IGF-1; IGF-BPs; IGF-1 receptor; skeletal muscle

Results 1-7 (7)