Euro Mediterranean Institute of Science and Technology

Palermo, Italy

Euro Mediterranean Institute of Science and Technology

Palermo, Italy
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Rizzo M.,University of Palermo | Rizzo M.,Euro Mediterranean Institute of Science and Technology | Rizzo M.,University of South Carolina | Barylski M.,Medical University of Lódz | And 4 more authors.
Current Pharmaceutical Design | Year: 2013

As the population becomes more obese and the prevalence of diabetes and the metabolic syndrome increases, low-density lipoprotein-cholesterol (LDL-C) may lose its value as a sole predictor for cardiovascular risk among lipids. Combined dyslipidemia is typically characterized by elevations in LDL-C and triglyceride levels, often accompanied by decreased high-density lipoproteincholesterol (HDL-C) concentrations and increased levels of small, dense LDL. This common disorder results from overproduction of hepatically synthesized apolipoprotein B in very low-density lipoproteins. In the last few years most of the international scientific guidelines as well as several expert panels have confirmed that LDL-C represents the primary or even the only target of treatment. Yet, increasing evidence suggests moving away from a LDL-C target-based approach to a more tailored treatment approach. For example, non- HDL-C has been introduced in the last few years as a target of treatment. © 2013 Bentham Science Publishers.


Garcia-Rios A.,University of Cordoba, Spain | Nikolic D.,University of Palermo | Perez-Martinez P.,University of Cordoba, Spain | Lopez-Miranda J.,University of Cordoba, Spain | And 3 more authors.
Current Pharmaceutical Design | Year: 2014

Low-density lipoproteins (LDL) are considered as important risk factors for cardiovascular diseases (CVD), while highdensity lipoproteins (HDL) are well recognized for their putative role in reverse cholesterol transport and other atheroprotective functions. Both LDL and HDL are heterogeneous in nature, including various subfractions depending on the method of isolation (_ 7 LDL and 10 HDL subspecies, respectively). While it is established that small, dense LDL (sdLDL) have atherogenic potential, the role of different HDL subfractions is still largely unclear. The majority of clinical studies suggest an atheroprotective role of larger HDL particles, although recent work has highlighted the role of dysfunctional HDL within different subfractions. Several therapeutic approaches are able to primarily target cholesterol concentration in LDL or HDL. Certain drugs, such as niacin, statins and fibrates target multiple lipid traits (i.e. pleiotropic drug effects), while cholesterol ester transfer protein (CETP) inhibitors are able to increase plasma HDL cholesterol levels. Statins represent the most used lipid-lowering drugs, but there is a continued interest in the development of novel therapeutic approaches, including those that might affect dysfunctional HDL. Targeting distinct LDL and HDL subfractions may potentially reduce the residual risk seen in clinical endpoint trials. © 2014 Bentham Science Publishers.


Katsiki N.,Aristotle University of Thessaloniki | Nikolic D.,University of Palermo | Montalto G.,University of Palermo | Banach M.,Medical University of Lódz | And 3 more authors.
Current Pharmaceutical Design | Year: 2013

Dyslipidemia, and especially atherogenic dyslipidemia, a combination of small low-density lipoproteins cholesterol (LDL-C), decreased high-density lipoprotein cholesterol (HDL-C) and increased triglyceride (TG) concentrations, represents a major cardiovascular (CV) risk factor. Nuclear receptor peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of lipid metabolism; PPAR ligands are used to treat dyslipidemias. Fibrates have a major impact on TG metabolism as well as on modulating LDL size and subclasses. Fibrates target atherogenic dyslipidemia by increasing plasma HDL-C concentrations and decreasing small dense LDL (sdLDL) particles and TGs, thus contributing to dyslipidemia management, particularly in patients with diabetes (DM) or the metabolic syndrome (MetS). Furthermore, fibrates exert beneficial effects on adipokines, inflammation and oxidative stress as well as neuroprotective properties. However, further studies are needed to define the role of fibrates in the prevention of CV events. We review the effects of fibrates on atherogenic dyslipidemia and CV risk reduction. © 2013 Bentham Science Publishers.


Banach M.,Medical University of Lódz | Rizzo M.,University of Palermo | Rizzo M.,Euro Mediterranean Institute of Science and Technology | Obradovic M.,University of Belgrade | And 4 more authors.
Current Pharmaceutical Design | Year: 2013

Plasma low-density lipoprotein cholesterol (LDL-C) is one of the biomarkers of cardiovascular disease (CVD) risk. LDL is cleared from the circulation preferentially through the LDL receptor (LDLR) pathway. Proprotein convertase subtilisin/kexin 9 (PCSK9) promotes the degradation of the LDLR. PCSK9 inhibition is attractive as a new strategy for lowering LDL-C levels, especially in combination with lipid lowering drugs such as statins. We review data from the available studies which focus on PCSK9 as a potential target in the treatment of hyperlipidemia. Further studies are still necessary to investigate the potential underlying mechanisms involved. © 2013 Bentham Science Publishers.


Barylski M.,Medical University of Lódz | Nikolic D.,University of Palermo | Rizzo M.,University of Palermo | Rizzo M.,Euro Mediterranean Institute of Science and Technology | And 2 more authors.
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2014

The first observations linking a low serum level of HDL-C to increased risk for cardiovascular disease were made over 50 years ago. High serum levels of HDL-C appear to protect against the development of atherosclerotic disease, while low serum levels of this lipoprotein are among the most important predictors of atherosclerotic disease in both men and women and people of all racial and ethnic groups throughout the world. It has long been assumed that therapeutic interventions targeted at raising HDL-C levels would lower risk for such cardiovascular events as myocardial infarction, ischemic stroke, and death. Even after five decades of intensive investigation, evidence to support this assumption has been fleeting. A number of post hoc analyses of randomized controlled trials and meta-analyses suggest that HDL-C raising, particularly when coupled with aggressive LDL-C reduction, impacts risk for cardiovascular events and rates of progression of atherosclerotic disease. Unfortunately, four recent prospective trials performed with the intent of testing the "HDL hypothesis" (ILLUMINATE, dal-OUTCOMES, AIM-HIGH, and HPS2-THRIVE) failed to meet their primary composite endpoints. These results have lead many clinicians and investigators to question the validity of the assumption that HDL-C raising reduces risk for cardiovascular events. Additional trials with other drugs are underway. In the meantime, HDL-C cannot be considered a target of therapy. Given the complexity of the HDL proteome and lipidome, there is biological plausibility for how HDL particles might exert atheroprotection. We explore the evidence supporting the inverse relationship between HDL-C and cardiovascular disease risk, documented mechanisms by which HDL particles may exert atheroprotection, and the findings either supporting or negating specific therapeutic interventions in patients afflicted with low HDL-C. © 2013 Elsevier Ltd. All rights reserved.


Barylski M.,Medical University of Lódz | Nikolic D.,University of Palermo | Banach M.,Medical University of Lódz | Rizzo M.,University of Palermo | And 2 more authors.
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2014

High-density lipoprotein (HDL) particles are highly complex polymolecular aggregates capable of performing a remarkable range of atheroprotective functions. Considerable research is being performed throughout the world to develop novel pharmacologic approaches to: (1) promote apoprotein A-I and HDL particle biosynthesis; (2) augment capacity for reverse cholesterol transport so as to reduce risk for the development and progression of atherosclerotic disease; and (3) modulate the functionality of HDL particles in order to increase their capacity to antagonize oxidation, inflammation, thrombosis, endothelial dysfunction, insulin resistance, and other processes that participate in arterial wall injury. HDL metabolism and the molecular constitution of HDL particles are highly complex and can change in response to both acute and chronic alterations in the metabolic milieu. To date, some of these interventions have been shown to positively impact rates of coronary artery disease progression. However, none of them have as yet been shown to significantly reduce risk for cardiovascular events. In the next 3-5 years a variety of pharmacologic interventions for modulating HDL metabolism and functionality will be tested in large, randomized, prospective outcomes trials. It is hoped that one or more of these therapeutic approaches will result in the ability to further reduce risk for cardiovascular events once low-density lipoprotein cholesterol and non-HDL-cholesterol targets have been attained. © 2013 Elsevier Ltd. All rights reserved.


Nikolic D.,University of Palermo | Katsiki N.,Aristotle University of Thessaloniki | Montalto G.,University of Palermo | Isenovic E.R.,University of Belgrade | And 2 more authors.
Nutrients | Year: 2013

Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS) are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in these subjects. Statins are the lipid-lowering drug of choice. Also, anti-obesity and lipid lowering drugs other than statins could be useful in these patients. However, the effects of anti-obesity drugs on CVD risk factors remain unclear. We review the clinical significance of sdLDL in being overweight and obesity, as well as the efficacy of anti-obesity drugs on LDL subfractions in these individuals; a short comment on HDL subclasses is also included. Our literature search was based on PubMed and Scopus listings. Further research is required to fully explore both the significance of sdLDL and the efficacy of anti-obesity drugs on LDL subfractions in being overweight, obesity and MetS. Improving the lipoprotein profile in these patients may represent an efficient approach for reducing cardiovascular risk. © 2013 by the authors; licensee MDPI, Basel, Switzerland.


Banerjee Y.,Sultan Qaboos University | Santos R.D.,University of Sao Paulo | Al-Rasadi K.,Sultan Qaboos University | Rizzo M.,University of Palermo | Rizzo M.,Euro Mediterranean Institute of Science and Technology
Atherosclerosis | Year: 2016

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) regulates the expression of low-density lipoprotein (LDL)-receptors, through reducing their recycling by binding to the receptor along with LDL and targeting it for lysosomal destruction. PCSK9 also enhances the degradation of very-low-density-lipoprotein receptor (VLDLR) and lipoprotein receptor-related protein 1 (LRP-1) in a LDL-receptor independent manner. This role in lipid homeostasis presents PCSK9 as an attractive target for the therapeutic management of familial hypercholesterolemia as well as other refractory dyslipidaemias. However, PCSK9 mediates multifarious functions independent of its role in lipid homeostasis, which can be grouped under "pleiotropic functions" of the protein. This includes PCSK9's role in: trafficking of epithelial sodium channel; hepatic regeneration; pancreatic integrity and glucose homeostasis; antiviral activity; antimalarial activity; regulation of different cell signalling pathways; cortical neural differentiation; neuronal apoptosis and Alzheimer's disease. The question that needs to be investigated in depth is "How will the pleotropic functions of PCSK9, be affected by the therapeutic intervention of the protease's LDL-receptor lowering activity?" In this review, we appraise the different lipid lowering strategies targeting PCSK9 in light of the protein's different pleiotropic functions. Additionally, we delineate the key areas that require further examination, to ensure the long-term safety of the above lipid-lowering strategies. © 2016 Elsevier Ireland Ltd.


Nibali L.,University College London | Tatarakis N.,University College London | Needleman I.,University College London | Tu Y.-K.,National Taiwan University | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Background: Several epidemiological studies have reported an association between metabolic syndrome (MetS) and periodontal diseases (PDs). The aim of this systematic review was to investigate the existence and magnitude of this association. Materials and Methods: A systematic search of the literature was conducted looking for casecontrol, cross-sectional, cohort studies and population surveys including patients with measures of MetS and PD. Ovid MEDLINE, EMBASE, LILACS, and Cochrane library databases were used for the search by 2 independent reviewers. A meta-analysis was conducted to investigate the association for coexistence of MetS and PD. Results: A total of 20 studies were included in the review, from an initial search of 3486 titles. Only 1 study reported longitudinal data on the onset of MetS components in association with periodontal measures. However, several studies investigated coexistence. A random effects meta-analysis showed that the presence of MetS is associated with the presence of periodontitis in a total of 36 337 subjects (odds ratio=1.71;95%confidence interval=1.42 to 2.03). When only studies with "secure" diagnoses wereincluded (n=16 405), themagnitudeof association increased (odds ratio=2.09;95%confidence interval = 1.28 to 3.44). Moderate heterogeneity was detected (I2 = 53.6%; P = .004). Conclusions: This review presents clear evidence for an association between MetS and periodontitis. The direction of the association and factors influencing it should be investigated by longitudinal and treatment studies. Periodontal diagnostic procedures should be routinely carried out in MetS patients. Copyright © 2013 by The Endocrine Society.


Tevy M.F.,Barcelona Institute for Research in Biomedicine | Giebultowicz J.,Oregon State University | Pincus Z.,Yale University | Mazzoccoli G.,IRCCS Scientific Institute and Regional General Hospital Casa Sollievo della Sofferenza | And 2 more authors.
Trends in Endocrinology and Metabolism | Year: 2013

The circadian clock machinery orchestrates organism metabolism to ensure that development, survival, and reproduction are attuned to diurnal environmental variations. For unknown reasons, there is a decline in circadian rhythms with age, concomitant with declines in the overall metabolic tissue homeostasis and changes in the feeding behavior of aged organisms. This disruption of the relationship between the clock and the nutrient-sensing networks might underlie age-related diseases; overall, greater knowledge of the molecular mediators of and variations in clock networks during lifespan may shed light on the aging process and how it may be delayed. In this review we address the complex links between the circadian clock, metabolic (dys)functions, and aging in different model organisms. © 2012 Elsevier Ltd.

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