Hyperlipidemias: Italy

Poli A, Marangoni F, Paoletti R, Mannarino E, Lupattelli G, Notarbartolo A, Aureli P, Bernini F, Cicero A, Gaddi A, Catapano A, Cricelli C, Gattone M, Marrocco W, Porrini M, Stella R, Vanotti A, Volpe M, Volpe R, Cannella C, Pinto A, Del Toma E, La Vecchia C, Tavani A, Manzato E, Riccardi G, Sirtori C, Zambon A, Anonymous00119. · Nutrition Foundation of Italy, Italy. · Nutr Metab Cardiovasc Dis. · Pubmed #18258418 No free full text.

Abstract: The importance of non-pharmacological control of plasma cholesterol levels in the population is increasing, along with the number of subjects whose plasma lipid levels are non-optimal, or frankly elevated, according to international guidelines. In this context, a panel of experts, organized and coordinated by the Nutrition Foundation of Italy, has evaluated the nutritional and lifestyle interventions to be adopted in the control of plasma cholesterol levels (and specifically of LDL cholesterol levels). This Consensus document summarizes the view of the panel on this topic, with the aim to provide an updated support to clinicians and other health professionals involved in cardiovascular prevention.

Gaddi A, Galetti C, Pauciullo P, Arca M. · Centro per lo Studio dell'Arteriosclerosi e delle Malattie Dismetaboliche Giancarlo Descovich, Servizio di Gerontologia, Policlinico S. Orsola-Malpighi, Bologna, Italy. · Nutr Metab Cardiovasc Dis. · Pubmed #10765523 No free full text.

Abstract: The Atherosclerosis and Dysmetabolic Disorders Study Group, headed by Prof. Rodolfo Paoletti, decided in 1994 to compose a committee of experts to formulate a clear description of familial combined hyperlipoproteinemia (FCH), a disorder illustrated in the literature, but still unknown to most physicians in spite of its severity and relative diffusion. The Committee consists of experts from the Lipid Clinics of the Universities of Ancona, Bari, Bologna, Ferrara, Genoa, Milan, Naples, Padua, Palermo, Perugia, Rome, Sassari, Turin, Verona and Venice. It has held several meetings coordinated by the national secretary at the "Giancarlo Descovich" Atherosclerosis Centre of the University of Bologna. This paper summarizes its conclusions.

Panza F, Solfrizzi V, D'Introno A, Colacicco AM, Santamato A, Seripa D, Pilotto A, Capurso A, Capurso C. · Department of Geriatrics, Center for Lipoprotein Metabolism, University of Bari, Policlinico, Piazza Giulio Cesare, 11, 70124 Bari, Italy. · Neurobiol Aging. · Pubmed #18179846 No free full text.

This publication has no abstract.

Grassi G, Taddei S. · Clinica Medica, University of Milano-Bicocca, Ospedale San Gerardo, Monza, Milano, Italy. · J Hypertens. · Pubmed #11330868 No free full text.

This publication has no abstract.

Parazzini F, Ricci E, Chiaffarino F, Trinchieri A. · Clinica Mangiagalli, Università degli Studi di Milano e Fondazione Policlinico-Mangiagalli-Regina Elena, Milano, Italy. · Arch Ital Urol Androl. · Pubmed #19499755 No free full text.

Abstract: In this narrative review we have briefly revised the main epidemiological evidences on the relation between erectile dysfunction (ED) and cardiovascular risk factors and diseases. There are consistent epidemiological evidences which link ED and cardiovascular diseases, diabetes or cholesterol levels. Most of studies which have taken into account in the analysis of the relation between ED and hypertension, cardiovascular diseases, smoking and weight (or body mass index) have shown that these factors have an independent role on the risk of ED. Otherwise, ED is a risk factor for subsequent development of cardiovascular diseases. In the routine clinical practice the presence of ED should be considered a "marker" for the development of cardiovascular diseases. The physician should consider to ask each patient regarding the presence of ED in order to focus preventive measures.

Giorgi PL. · Università, Ancona. · Recenti Prog Med. · Pubmed #19445282 No free full text.

Abstract: Probiotics are defined viable microorganisms which in sufficient amount reach the intestine in an active state, to be able to exert positive health benefit on the host. Thus far, they have shown particular promise on prevention or treatment of various pathologic conditions. Our aim has been to report the most recent articles (until October 2008), resulting from randomized, double controlled trials, according to the conventional and molecular methods. In this review we have taken into consideration almost all the fields in which the probiotics have been given, either with a prophylactic or therapeutic intent. So far we have summarized the actual results concerning lactose intolerance, acute rotavirus diarrhea, traveller's diarrhea, antibiotic associated diarrhea, Clostridium difficile infection, and the role as adjuvant in Helicobacter pylori eradication. Furthermore, we have synthesised articles concerning the probiotic connection in irritable bowel syndrome, and in inflammatory bowel diseases. Last but not least, the prevention by probiotics of allergic diseases, of bacterial vaginosis, of respiratory infections, and the possible advantage in hypercholesteremic subjects.

Giannattasio C, Failla M, Corsi D, Capra A, Meles E, Gentile G, Fantini E, Boffi L, Maestroni S, Scotti V, Mancia G. · Clinica Medica, Università degli Studi di Milano-Bicocca, Ospedale San Gerardo, Monza, MI. · Ital Heart J Suppl. · Pubmed #19400052 No free full text.

Abstract: The reduction of large arterial distensibility has several adverse consequences for the cardiovascular system. This paper reviews the evidence we have obtained by measuring distensibility through quantification of changes in arterial diameter vs blood pressure changes at large elastic and middle size muscle artery sites. Evidence shows that arterial distensibility is reduced in conditions such as hypercholesterolemia, hypertension, diabetes, and congestive heart failure. In some conditions (e.g. hypertension) the alterations are not uniformly distributed in the arteries of different structure and size whereas in others (e.g. diabetes and heart failure) they are widespread. In diabetes evidence is available that distensibility changes occur early in the course of the disease. Evidence is also available that in all above conditions treatment can improve arterial distensibility thereby reversing the initial abnormality. This is due to a variable combination of structural and functional factors. However, technical ability to determine their precise role in distensibility changes in humans is limited.

Marchetti F, Cannioto Z. · Clinica Pediatrica, IRCCS Burlo Garofalo, Università, Trieste. · Recenti Prog Med. · Pubmed #19388217 No free full text.

Abstract: The recommendation of statin treatment to younger patients too, as recently issued by the American Academy of Pediatrics, appeared to be controversial, especially looking at the lack of evidence in term of efficacy on primary end-point and long term safety data.

Corsini A, Windler E, Farnier M. · Department of Pharmacological Sciences, University of Milan, Milan, Italy. · Eur J Cardiovasc Prev Rehabil. · Pubmed #19237992 No free full text.

Abstract: Several recent meta-analyses of numerous lipid-lowering outcome trials confirm the direct relationship between low-density lipoprotein-cholesterol (LDL-C) lowering and cardiovascular risk reduction. As a consequence, LDL-C goals are continuously being set lower. To achieve lipid lowering, several efficient drugs are available, however, the current pharmacopoeia remains limited for some critical patient situations. Colesevelam hydrochloride is a specifically engineered bile acid sequestrant that features a more favourable tolerability and drug interaction profile than traditional bile acid sequestrants, because of a better affinity and binding capacity to bile acids. In addition, colesevelam retains the nonsystemic mode of action of bile acid sequestrants. Moreover, colesevelam lowers LDL-C by 15-19% and 10-16%, respectively, in monotherapy and in combination to various lipid-lowering drugs, such as statins, ezetimibe and fenofibrates. Along with an efficient and sustainable effect on lipid profiles, colesevelam - as other bile acid sequestrants - has been shown to lower the glycosylated haemoglobin HbA1c by 0.5% on average in patients with type 2 diabetes. Overall, colesevelam represents an interesting add-on treatment to be used in high-risk patients with hypercholesterolaemia for whom standard lipid-lowering therapies are not enough or not well tolerated.

Rizzo M, Berneis K, Spinas GA, Rini GB, Kapur NK. · Department of Internal Medicine and Emerging Diseases, University of Palermo, Palermo, Italy. · Int J Clin Pract. · Pubmed #19222633 No free full text.

Abstract: BACKGROUND: Statins have emerged as the global leader in pharmacologic therapy for dyslipidaemia, and rosuvastatin has demonstrated clinical efficacy as well as safety in several clinical trials and postmarketing analyses. AIM: The present article reviewed the effects of rosuvastatin on the quantity and the quality of low-density lipoproteins (LDL). METHODS: We searched for and reviewed all the available evidence in a systematic way. A literature search (by Medline and Scopus) was performed using the following headings: 'LDL-cholesterol', 'LDL size', 'LDL subclasses', 'small dense LDL', 'apolipoprotein B, apo B' and 'rosuvastatin' up to 11 November 2008. The authors also manually reviewed the references of selected articles for any pertinent material. RESULTS: Rosuvastatin reduces LDL-cholesterol levels to a greater extent than other statins and is able to modulate significantly LDL size and subclasses towards less atherogenic particles as well as the LDL particle number, as indirectly measured by the levels of apo B. DISCUSSION AND CONCLUSIONS: The recent Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin study provides more evidence about the effectiveness of rosuvastatin therapy in reducing cardiovascular risk, even among persons who would not currently be considered for pharmacotherapy. Further insights on cardiovascular outcomes will be available by the on-going trials included in the GALAXY program that includes subjects with type-2 diabetes, haemodialysis recipients, patients with congestive heart failure and specific ethnic groups, such as African American, Hispanic and South Asian populations.

Stefani M, Liguri G. · Department of Biochemical Sciences and Research Centre on Neurodegeneration (CIMN), University of Florence, Florence, Italy. · Curr Alzheimer Res. · Pubmed #19199871 No free full text.

Abstract: The role of cholesterol as a susceptibility factor or a protective agent in neurodegeneration and, more generally, in amyloid-induced cytotoxicity is still controversial. Epidemiological studies on the hypercholesterolemia-AD risk relation and some reports indicating a beneficial effect of statin therapy suggest cholesterol as a susceptibility factor in AD. The ApoE4 genotype as a prevalent genetic risk factor for AD and the function of ApoE as main cholesterol carrier in the brain also underlie a close cholesterol load-AD risk relation. Finally, cell biology evidences support a critical involvement of lipid raft cholesterol in the modulation of beta- and gamma-secretase cleavage of APP with altered Abeta production. However, little exchange does exist between circulating and brain cholesterol, the latter arising from endogenous synthesis. In addition, increasing evidence supports the idea that amyloid cytotoxicity in most cases is initiated by oligomer recruitment at the cell membrane with loss of membrane integrity, Ca(2+) ingress into the cell, oxidative stress and apoptosis. In such a scenario, increased membrane cholesterol seems to be protective by disfavouring aggregate binding to the membrane. Recent findings also indicate that a reduction of cellular cholesterol favours co-localization of BACE1 and APP in non-raft membrane domains and hinders generation of plasmin, an Abeta-degrading enzyme. Finally, recent researches on Seladin-1, involved in cholesterol biosynthesis, show that modulation of membrane cholesterol affects Abeta generation and cell resistance against Abeta oligomer toxicity. These data confirm previous findings indicating a reduction of the cholesterol/phospholipid ratio in aged and AD brains. The aim of this review is to critically discuss some of the main results reported in the recent years in this field supporting a role of cholesterol either as a susceptibility factor or as a protective agent in AD.

Cravedi P, Ruggenenti P, Remuzzi G. · Department of Medicine and Transplantation, Ospedali Riuniti di Bergamo, Mario Negri Institute for Pharmacological Research, Bergamo, Italy. · J Ren Care. · Pubmed #19160879 No free full text.

Abstract: The level of proteinuria is one of the most important predictors for progressive renal function loss in kidney disease. Reduction of urinary protein levels by renin-angiotensin-system (RAS) inhibitors limits renal function decline in patients with non-diabetic and diabetic nephropathies to the point that remission of the disease and regression of renal lesions have been reported. The increasing use of these drugs is possibly at the basis of the stabilization of rates of new cases of kidney failure reported to the US Renal Data System after a 2-decade period of progressive increases. RAS inhibition, however, may not be effective to the same degree in all patients. For those patients who do not reach a complete remission of proteinuria, treatment procedures to implement renoprotection should include strict blood pressure control (and metabolic control in diabetics), lowering of blood lipids, and lifestyle modifications. Early intervention may be important to maximize renoprotection, especially in diabetics.

Pirro M, Bagaglia F, Paoletti L, Razzi R, Mannarino MR. · Medicina Interna, Angiologia e Malattie da Arteriosclerosi, Università degli Studi di Perugia, Ospedale S. Maria della Misericordia, Perugia, Italy. · Ther Adv Cardiovasc Dis. · Pubmed #19124431 No free full text.

Abstract: Hypercholesterolemia has been associated with increased cardiovascular risk by contributing to mechanical endothelial injury and dysfunction. There is evidence that chronic exposure to increased plasma cholesterol levels might also impair the repair of lipoprotein-mediated endothelial injury, possibly by reducing the availability and function of circulating endothelial progenitors. This review summarizes current knowledge about the mechanisms of lipoprotein-mediated endothelial injury and endothelial progenitor cell assisted vascular repair; the influence of hypercholesterolemia on endothelial progenitor cell dysfunction will be also addressed.

Cravedi P, Remuzzi G. · Clinical Research Centre for Rare Diseases Aldo e Cele Daccò, Mario Negri Institute for Pharmacological Research, Villa Camozzi, Ranica, Bergamo, Italy. · Kidney Int Suppl. · Pubmed #19034321 No free full text.

Abstract: The incidence of chronic renal and cardiovascular diseases is increasing worldwide. Since renal disease is the strongest risk factor for cardiovascular morbidity and mortality, strategies able to reduce renal disease progression are expected to translate into a decreased incidence of cardiovascular events. To this purpose, inhibition of the renin-angiotensin system, both by angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists, represents the best available option. Several large, randomized studies have convincingly shown that these treatments are associated with a significant reduction in the risk for renal disease progression in diabetic and non diabetic patients with chronic kidney disease. Importantly, improvement of renal outcomes is paralleled by a reduction of the cardiovascular risk. However, a significant proportion of patients with chronic nephropathies still progresses to end-stage renal failure or dies for cardiovascular events. A more complex strategy, including strict control of BP and proteinuria, lowering of blood lipids, tight metabolic control of diabetes, and lifestyle changes may improve morbidity and mortality of patients with chronic renal disease as compared with single or dual intervention on the renin-angiotensin system. Moreover, prevention strategies are urgently needed to face the burden of chronic renal disease and cardiovascular morbidity and mortality. This is particularly true for developing countries, where the incidence of these chronic diseases is growing with the highest rate.

Di Castelnuovo A, Quacquaruccio G, Donati MB, de Gaetano G, Iacoviello L. · Laboratory of Genetic and Environmental Epidemiology, Research Laboratories, John Paul II Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy. · Am J Epidemiol. · Pubmed #18845552 No free full text.

Abstract: Spousal pairs permit assessment of determinants of diseases related to environment, because they share the same lifestyle and environment. The authors reviewed spouses' concordance for the major coronary risk factors. A search of the MEDLINE, PubMed, and EMBASE databases was performed. Seventy-one papers were selected for a total of 207 cohorts of pairs and 424,613 correlations in more than 100,000 couples. The most strongly correlated within-pairs factors were smoking and body mass index, with overall correlations of 0.23 (95% confidence interval: 0.12, 0.36) and 0.15 (95% confidence interval: 0.05, 0.25), respectively. Statistically significant positive correlations were also found for diastolic blood pressure, triglycerides, total and low density lipoprotein cholesterol, weight, and the waist/hip ratio. The overall odds ratios for concordance in hypertension, smoking, diabetes, and obesity were all statistically significant, ranging from 1.16 to 3.25. Assortative mating influenced concordance for blood pressure, smoking, glucose, low density lipoprotein cholesterol, weight, body mass index, and waist circumference. This systematic review shows a statistically significant positive spousal concordance for the majority of main coronary risk factors. However, the strength of the concordance was markedly different among factors and appeared to be quite modest for all of them. Interventions to reduce cardiovascular risk factors should be addressed jointly to both members of a marital couple.

Sorrentino G, Migliaccio R, Bonavita V. · University of Naples 'Parthenope', Naples, Italy. · Eur Neurol. · Pubmed #18756085 links to  free full text

Abstract: Vascular dementia (VaD), rather than being considered as a univocal nosological entity, should be regarded as a heterogeneous clinical entity which differs in clinical-pathological phenotype as well as in pathophysiological mechanisms, but shares cerebrovascular disease (CVD), resulting from vascular or circulatory pathology, as the cause of dementia. The aim of this review is to discuss VaD treatment focusing particularly on more prevalent ischemic forms. Due to the fact that there are presently no treatments capable of obtaining considerable results once VaD is clinically established, specific emphasis will be given to the therapeutic strategies aimed at the prevention of CVD risk factors. The therapeutic strategies aimed at slowing the progression of the disease will also be discussed.

Grigore L, Norata GD, Catapano AL. · Department of Pharmacological Sciences, University of Milan, Milan, Italy. · Vasc Health Risk Manag. · Pubmed #18561502 links to  free full text

Abstract: Although widely used in lipid lowering therapy, HMG CoA reductase inhibitors (even when administered at high doses) are frequently insufficient to achieve guideline-recommended LDL-C goals for many patients with hypercholesterolemia in everyday clinical practice. Many patients do not achieve LDL-C goal on the initial dose of statin and the majority of these patients does not reach their goal after 6 months. As a consequence, a wide therapeutic gap exists between target LDL-C levels and those typically achieved in clinical practice. A recent and more effective therapeutic hypocholesterolemic strategy is to treat the two main sources of cholesterol simultaneously (production of cholesterol, mainly in the liver, and absorption of cholesterol in the intestine) with a complementary mechanism of action, by co-administering ezetimibe, a novel agent inhibiting cholesterol absorption, with a statin, which inhibits cholesterol production in the liver. Ezetimibe can be effectively and safely co-administered with any dose of any statin and, compared with the single inhibition of cholesterol production, afforded by statins alone, provides consistently greater reductions in LDL-C through dual inhibition of both cholesterol production and absorption. We summarize the pivotal role of both the liver and intestine in the overall balance of cholesterol in the body and describe the clinical impact and relevance of using ezetimibe either alone or co-administered with statins in controlling elevated levels of plasma LDL cholesterol.

Crosignani A, Battezzati PM, Invernizzi P, Selmi C, Prina E, Podda M. · Dipartimento di Medicina Interna, Polo Universitario, Ospedale San Paolo, Via di Rudini 8, Milano 20142, Italy. · World J Gastroenterol. · Pubmed #18528929 links to  free full text

Abstract: Primary biliary cirrhosis (PBC), which is characterised by progressive destruction of intrahepatic bile ducts, is not a rare disease since both prevalence and incidence are increasing during the last years mainly due to the improvement of case finding strategies. The prognosis of the disease has improved due to both the recognition of earlier and indolent cases, and to the wide use of ursodeoxycholic acid (UDCA). New indicators of prognosis are available that will be useful especially for the growing number of patients with less severe disease. Most patients are asymptomatic at presentation. Pruritus may represent the most distressing symptom and, when UDCA is ineffective, cholestyramine represents the mainstay of treatment. Complications of long-standing cholestasis may be clinically relevant only in very advanced stages. Available data on the effects of UDCA on clinically relevant end points clearly indicate that the drug is able to slow but not to halt the progression of the disease while, in advanced stages, the only therapeutic option remains liver transplantation.

Bergero D, Nery J. · DIPAEE, Grugliasco (TO), Italy. · J Anim Physiol Anim Nutr (Berl). · Pubmed #18477316 No free full text.

Abstract: The concept 'liver disease' includes several pathological conditions affecting liver's functions. It can either consist of a temporary impaired functioning of the liver and/or it can progress to its failure. The purpose of this review is to update the knowledge on hepatobiliary diseases and in particular on equine hyperlipaemia. Hepatobiliary disease's aetiology, clinical signs, diagnosis and nutritional management are thus described in the first part of the review the second part being devoted to hyperlypaemia's lipid metabolism, epidemiology, clinical signs, post-mortem observations and nutritional management. Diagnosis of hepatic disease is usually based on the assessment of the serum activities while hepatic biopsy is considered as the golden standard of diagnosis of hepatic function. Nutritional management is often very useful in management of hepatic diseases: diet should be low in protein (of good biological value) and high in non-structural carbohydrates except for chronic hepatic disease (slightly high protein). Equine hyperlipaemia's mortality is around 70%. It consists of a disorder of lipid metabolism, characterized by increase in plasma triglycerides and deposition of fat on organs. From a nutritional point of view, hyperlipaemia in horses can be approached by maintaining positive energy balance, fighting dehydration and metabolic acidosis, and by the use of lipotropic factors.

Alonzi T, Mancone C, Amicone L, Tripodi M. · National Institute for Infectious Diseases, L. Spallanzani, IRCCS, Rome, Italy. · Expert Rev Proteomics. · Pubmed #18282126 No free full text.

Abstract: Lipoproteins are responsible for lipid packaging and transport through the bloodstream, and for their delivery to target tissues. Their participation in process, such as inflammation and innate immunity has also been suggested recently. Lipoprotein particles have very complex biochemical structures, which result from intricate processes involving coordinated mechanisms of protein and lipid synthesis, intracellular assembling and trafficking, and intra- and extracellular metabolism. Alterations in these mechanisms cause several negative effects on human health. The ability of current proteomic approaches to dissect the dynamic nature of complex particles revealing protein composition and post-translational modifications is shedding further light on lipoprotein structures and functions. This review summarizes lipoprotein classification, biogenesis and metabolism as well as discussing how the results of 20 proteomics-based reports integrate our knowledge on both their biochemical composition and their effects on target cells, thus contributing to reveal the possible functions.

Puccetti L, Acampa M, Auteri A. · Department of Clinical Medicine and Immunological Sciences, Section of Internal Medicine, University of Siena, Siena, Italy. · Recent Pat Cardiovasc Drug Discov. · Pubmed #18221122 No free full text.

Abstract: Cardiovascular disease has become the global leading cause of death worldwide, representing the most frequent cause of morbidity and mortality in the developed world. Statins, the most widely prescribed cholesterol-lowering drugs, are considered to be first-line therapeutics for the prevention of coronary heart disease and atherosclerosis. Meta-analyses from several primary and secondary intervention studies have clearly shown that cholesterol-lowering medication, significantly reduces cardiovascular events, mortality, and morbidity, but considerable interindividual variation exists in response to statin therapy. Pharmacogenomics can provide important insights into statins therapy through elucidation of the genetic (or genomic) contribution to variable response for these drugs. The search for genetic polymorphisms may enable us to identify novel determinants of drug responsiveness by means of the study of three candidate genes groups: (1) genes encoding proteins involved in metabolism or drug transport, or both, that influence drug pharmacokinetics; (2) genes encoding proteins involved in mechanism of action and/or metabolic pathways on which drugs operate (that influence pharmacodynamics); (3) genes encoding proteins involved in the underlying disease condition or intermediate phenotype. This review briefly summarizes the recent pharmacogenomic and pharmacogenetic patents and the potential contributions of genetic variations in candidate genes related to lipid and lipoprotein metabolism and statins efficacy.

Gaddi A, Cicero AF, Odoo FO, Poli AA, Paoletti R, Anonymous00278. · Center for Metabolic diseases and Atherosclerosis, University of Bologna, Italy. · Vasc Health Risk Manag. · Pubmed #18200807 links to  free full text

Abstract: Familial combined hyperlidemia (FCH) is a common metabolic disorder characterized by: (a) increase in cholesterolemia and/or triglyceridemia in at least two members of the same family, (b) intra-individual and intrafamilial variability of the lipid phenotype, and (c) increased risk of premature coronary heart disease (CHD). FCH is very frequent and is one of the most common genetic hyperlipidemias in the general population (prevalence estimated: 0.5%-2.0%), being the most frequent in patients affected by CHD (10%) and among acute myocardial infarction survivors aged less than 60 (11.3%). This percentage increases to 40% when all the myocardial infarction survivors are considered without age limits. However, because of the peculiar variability of laboratory parameters, and because of the frequent overlapping with the features of metabolic syndrome, this serious disease is often not recognized and treated. The aim of this review is to define the main characteristics of the disease in order to simplify its detection and early treatment by all physicians by mean of practical guidelines.

Onofrillo D, Accorsi P. · Dipartimento di Medicina Trasfusionale, Ospedale Civile Pescara, Pescara, Italy. · Transfus Apher Sci. · Pubmed #18054286 No free full text.

This publication has no abstract.

Santilli F, Basili S, Ferroni P, Davì G. · Center of Excellence on Aging, University of Chieti "G. D'Annunzio" School of Medicine, Via Colle dell'Ara, I-66013, Chieti, Italy. · Intern Emerg Med. · Pubmed #18043876 No free full text.

Abstract: Several distinct lines of investigation in the context of atherosclerosis dealing with low-grade inflammation, oxidative stress and platelet activation are now emerging, with CD40/CD40L system as the missing link. CD40 ligand is a transmembrane glycoprotein structurally related to tumour necrosis factor-alpha and more than 95% of the circulating CD40L derives from platelets. CD40L appears as a multiplayer of several cell types in the inflammatory network. The peculiarity of CD40L as an inflammatory mediator derived from platelets expands the functional repertoire of platelets from players of haemostasis and thrombosis to powerful amplifiers of inflammation by promoting the release of cytokines and chemokines, cell activation and cell-cell interactions. The multifunctional role of CD40L, as a simultaneous activator of all these systems, further blurs the intricate relationship between such events both in the physiological systems and the pathological derangement occurring in atherothrombosis.

Catapano AL. · Center for the Study of Atherosclerosis and Laboratory of Lipoprotein Metabolism, Department of Pharmacological Sciences, University of Milan, Milan, Italy. · Fundam Clin Pharmacol. · Pubmed #18001316 No free full text.

Abstract: The recent discoveries on the concerted role of several mechanisms involved in regulating the balance of body cholesterol highlight the role of intestinal absorption. Selective modulators of intestinal cholesterol absorption are available that offer a new pharmacologic approach to the modulation of total body cholesterol homeostasis and to a more effective reduction of low-density-lipoprotein cholesterol.