Hyperlipidemias: France

Staels B. · Universite Lille Nord de France, Inserm U545, UDSL, Lille, France. · Postgrad Med. · Pubmed #19494475 No free full text.

Abstract: Clinical evidence has demonstrated that bile acid sequestrants reduce glucose levels in patients with type 2 diabetes mellitus (T2DM). This effect has been confirmed in multiple double-blind, placebo-controlled clinical studies with the bile acid sequestrant colesevelam hydrochloride (HCl). Colesevelam HCl was approved by the US Food and Drug Administration in January 2008 as an adjunctive therapy for patients with T2DM to improve glycemic control. However, the mechanism of action for the glucose-lowering effect of bile acid sequestrants is unclear. Bile acid sequestrants are nonsystemic pharmacological agents that bind bile acids in the gastrointestinal tract, thereby diverting bile acids from the enterohepatic circulation. This, in turn, upregulates bile acid synthesis (via cholesterol 7-alpha-hydroxylase), which utilizes cholesterol, resulting in reduced low-density lipoprotein cholesterol levels. Recent research has revealed that bile acids are tightly controlled signaling molecules that have metabolic effects beyond their primary role in bile to aid in the digestion of lipids and fat. Bile acids signal via various membrane and nuclear receptors. Therefore, bile acid sequestrants may exert glycemic effects by altering the interaction of these bile acid pathways. This article reviews the role for bile acids in glucose regulation and discusses the potential mechanism(s) of action for the glycemic effects of bile acid sequestrants.

Farnier M. · Endocrinologie maladies métaboliques, Point Médical, F-21000, Dijon, France. · Presse Med. · Pubmed #19376680 No free full text.

Abstract: Plasma lipids should - and can reliably - be measured within 24 hours of the onset of symptoms of acute coronary syndrome. They should again be measured from 1 to 3 months after the event. The level of low-density lipoproteins(LDL) cholesterol remains the marker for treatment initiation and for evaluation of therapeutic goals. The total number of atherogenic particles is a better determinant of cardiovascular risk than the LDL-cholesterol level, as are the levels of non-high-density lipoprotein (HDL)-cholesterol and apolipoprotein B. The use of apolipoprotein B by primary care physicians is limited by the lack of standardization and must be restricted to specific clinical cases. Non-HDL-cholesterol can be recommended as a secondary target in patients with high triglyceride levels. In coronary patients treated with a statin, management of abnormal levels of triglycerides and HDL-cholesterol is important to minimize the risk of recurrence.

Abifadel M, Rabès JP, Devillers M, Munnich A, Erlich D, Junien C, Varret M, Boileau C. · Institut Nationale de la Santé et de la Recherche Médicale (INSERM), U781, Paris, France. · Hum Mutat. · Pubmed #19191301 No free full text.

Abstract: Hypercholesterolemia is one of the major causes of coronary heart disease (CHD). The genes encoding the low-density lipoprotein receptor and its ligand apolipoprotein B, have been the two genes classically implicated in autosomal dominant hypercholesterolemia (ADH). Our discovery in 2003 of the first mutations of the proprotein convertase subtilisin kexin 9 gene (PCSK9) causing ADH shed light on an unknown actor in cholesterol metabolism that since then has been extensively investigated. Several PCSK9 variants have been identified, some of them are gain-of-function mutations causing hypercholesterolemia by a reduction of low-density lipoprotein (LDL) receptor levels; while others are loss-of-function variants associated with a reduction of LDL-cholesterol (LDL-C) levels and a decreased risk of CHD. In this review, we focus on reported variants, and their biological, clinical, and functional relevance. We also highlight the spectrum of hypercholesterolemia or hypobetalipoproteinemia phenotypes that are already associated with mutations in PCSK9. Finally, we present future prospects concerning this therapeutic target that might constitute a new approach to reduce cholesterol levels and CHD, and enhance the effectiveness of other lipid-lowering drugs.

Tazi J, Bakkour N, Stamm S. · University of Montpellier II, Institute of Molecular Genetics, Centre Nationale de Recherche Scientifique, 1919 Route de Mende, France. · Biochim Biophys Acta. · Pubmed #18992329 No free full text.

Abstract: Almost all protein-coding genes are spliced and their majority is alternatively spliced. Alternative splicing is a key element in eukaryotic gene expression that increases the coding capacity of the human genome and an increasing number of examples illustrates that the selection of wrong splice sites causes human disease. A fine-tuned balance of factors regulates splice site selection. Here, we discuss well-studied examples that show how a disturbance of this balance can cause human disease. The rapidly emerging knowledge of splicing regulation now allows the development of treatment options.

Zannad F, Agabiti-Rosei E. · Inserm, CIC 9501 et U684, CHU Nancy, France. · J Hypertens. · Pubmed #18815513 No free full text.

Abstract: In addition to the prevention and treatment of macro- and microvascular complications, management goals for patients with type 2 diabetes include reducing the risk of cardiovascular events with a view to improving quality of life. A number of epidemiological and observational cohort studies have been published in Italy and France in an effort to determine the patient profile of individuals with type 2 diabetes in these countries and to gather data on current clinical practice and prescribing patterns. The results of the studies confirm that cardiovascular risk factors, such as hypertension and elevated cholesterol, commonly occur in patients with type 2 diabetes and that these co-morbid conditions are not well controlled. As a consequence, both macro- and microvascular complications are prevalent in this patient population. It is clear that the management of type 2 diabetes in France and Italy is suboptimal. In both primary and specialist care, treatment guidelines need to be reinforced and a more aggressive approach needs to be adopted in the treatment of modifiable cardiovascular risk factors and in particular hypertension. Collectively, the available data highlight the importance of managing global cardiovascular risk within the context of diabetes care. Greater adherence to therapeutic targets recommended in guidelines will ensure that greater proportions of patients attain these treatment goals thereby reducing diabetes-related morbidity and mortality.

Gay G, Delvaux M, Frederic M. · Department of Internal Medicine and Digestive Pathology, CHU of Nancy, Hopitaux de Brabois, Allee du Morvan, Vandoeuvre les Nancy F-54511, France. · World J Gastroenterol. · Pubmed #18785273 links to  free full text

Abstract: Despite significant advances over the last decade, mucosal lesions of the small bowel are poorly detected by imaging studies such as CT scan, MRI-enteroclysis and contrast-enhanced abdominal ultrasound. Capsule endoscopy (CE) has dramatically changed the diagnostic approach to intestinal diseases. Moreover, the use of CE can be extended to include other conditions. However, it is difficult to assess the positive influence of CE on patient outcomes in conditions involving a small number of patients, or in critically ill and difficult to examine patients. CE has the advantage of diagnosing intestinal lesions and of directing the use of double balloon enteroscopy (DBE) in order to obtain biopsy specimens. Moreover, CE allows repeated assessment in chronic conditions, especially to detect relapse of an infectious disease.

Costet P, Krempf M, Cariou B. · INSERM, UMR915, L'Institut du Thorax, 1 Rue Gaston Veil, Nantes, France. · Trends Biochem Sci. · Pubmed #18672372 No free full text.

Abstract: Gain-of-function mutations within proprotein convertase subtilisin kexin type 9 (PCSK9) are linked to familial autosomal dominant hypercholesterolaemia, a disease characterized by elevated plasma concentrations of cholesterol associated with low-density lipoproteins (LDLs). Conversely, PCSK9 loss-of-function mutations result in low levels of LDL cholesterol (LDLC) and protect against coronary heart disease. Although compelling evidence indicates that PCSK9 impairs the LDLR pathway, its role in cholesterol metabolism remains incompletely defined. In the past two years, several new biochemical findings, including the PCSK9 crystal structure and the identification of several transcriptional repressors, were reported. Moreover, new clinical and epidemiological data have revealed the correlation between plasma PCSK9 concentrations and LDLC levels.

Staels B, Maes M, Zambon A. · Department of Atherosclerosis, Institut Pasteur de Lille, UMR545 Inserm, University of Lille 2, Lille, France. · Nat Clin Pract Cardiovasc Med. · Pubmed #18628776 No free full text.

Abstract: Statins lower cardiovascular risk in patients with diabetes; however, as these patients are at higher risk than other cardiovascular patients, statins merely decrease coronary event rates to the level seen in untreated nondiabetic individuals at risk for cardiovascular disease, indicating the existence of substantial residual risk. One reasonable explanation resides in the fact that statins have only limited effectiveness on hypertriglyceridemia and low HDL cholesterol, and they do not normalize the LDL size-distribution pattern. Peroxisome proliferator-activated receptor (PPAR)alpha agonists, which include fibrates, normalize this atherogenic lipid profile, as well as several cardiovascular risk markers associated with the metabolic syndrome and type 2 diabetes. In particular, hypertriglyceridemia and the ratio of small dense:large buoyant LDL particles are significantly improved. Outcome trials of PPARalpha agonists have demonstrated reductions in cardiovascular morbidity in patients with diabetes and in those with the metabolic syndrome; plaque progression is diminished, diabetic nephropathy and retinopathy are counteracted and amputation-risk decreased. The combination of fibrates with statins improves overall lipoprotein profile further. PPARalpha agonists seem particularly indicated in patients with diabetes who have residual dyslipidemia (high triglyceride and/or low HDL) despite receiving statin therapy, and patients who are nondiabetic, overweight, insulin-resistant and who have hypertriglyceridemia and/or low HDL cholesterol and chronic inflammation.

Duron E, Hanon O. · Broca Hospital, Paris, France. · Vasc Health Risk Manag. · Pubmed #18561512 links to  free full text

Abstract: Dementia is one of the most important neurological disorders in the elderly. Aging is associated with a large increase in the prevalence and incidence of degenerative (Alzheimer's disease) and vascular dementia, leading to a devastating loss of autonomy. In view of the increasing longevity of populations worldwide, prevention of dementia has turned into a major public health challenge. In the past decade, several vascular risk factors have been found to be associated with vascular dementia but also Alzheimer's disease. Some longitudinal studies, have found significant associations between hypertension, diabetus mellitus, and metabolic syndrome, assessed at middle age, and dementia. Studies assessing the link between hypercholesterolemia, atrial fibrillation, smoking, and dementia have given more conflicting results. Furthermore, some studies have highlighted the possible protective effect of antihypertensive therapy on cognition and some trials are evaluating the effects of statins and treatments for insulin resistance. Vascular risk factors and their treatments are a promising avenue of research for prevention of dementia, and further long-term, placebo-controlled, randomized studies, need to be performed.

Skilton MR. · Human Nutrition Research Centre, Université Claude Bernard, Lyon, France. · Pediatrics. · Pubmed #18310207 links to  free full text

Abstract: Evidence from noninvasive ultrasound studies of the neonatal aorta and fetal and early childhood postmortem studies indicates that impaired fetal growth, in utero exposure to maternal hypercholesterolemia, and diabetic macrosomia may all be important risk factors for vascular changes consistent with the earliest physical signs of atherosclerosis. Although the exact mechanisms that underlie these associations remain unclear, animal models have suggested that the use of antioxidant, lipid-lowering, and other innovative therapies may counteract the impact of these intrauterine risk factors for cardiovascular disease. This review summarizes the current evidence for intrauterine factors that have a direct impact on atherosclerosis and provides potential treatment and prevention strategies.

Varret M, Abifadel M, Rabès JP, Boileau C. · INSERM U781, Hôpital Necker-Enfants Malades, Université Paris 5 - René Descartes, Paris, France. · Clin Genet. · Pubmed #18028451 No free full text.

Abstract: Autosomal dominant hypercholesterolemia (ADH) is characterized by isolated elevation of plasmatic low-density lipoprotein cholesterol associated with high risk of premature cardiovascular complications. More than 1000 mutations in the LDLR gene and 9 in the APOB gene have been implicated. We have shown further heterogeneity with the discovery of missense mutations in the PCSK9 gene resulting in ADH. Different studies have tried to evaluate the respective contribution of mutations in each gene to the disease, but results were not always in agreement. After a brief overview of mutations reported for each gene, strategies and results of these different studies are reviewed and analyzed. Altogether, numerous reports give evidence for the existence of a greater level of genetic heterogeneity in ADH and the involvement of still unknown genes.

Farnier M. · Point Médical, Rond Point de la Nation, 21000 Dijon, France. · Fundam Clin Pharmacol. · Pubmed #18001317 No free full text.

Abstract: Ezetimibe with simvastatin in combination inhibits both the absorption and production of cholesterol. This dual mechanism of inhibition substantially increases the capacity to decrease levels of atherogenic low-density lipoproteins, compared with that observed when either drug is used alone. Ezetimibe/simvastatin is more effective than atorvastatin or rosuvastatin monotherapy treatments in low-density lipoprotein cholesterol lowering and getting more patients to goals. Ezetimibe/simvastatin offers an important treatment alternative to patients who respond inadequately even to high-dose statin therapy.

Vergès B. · Service d'Endocrinologie, Diabétologie et Maladies Métaboliques, Hôpital du Bocage, C.H.U. Dijon, France. · Fundam Clin Pharmacol. · Pubmed #18001314 No free full text.

Abstract: Both pioglitazone and rosiglitazone are effective hypoglycaemic agents in monotherapy as in combined therapy. Interestingly, their reducing effect on fasting glycaemia and HbA1c is maintained over time, suggesting a potential protective effect of glitazones on the pancreatic beta-cells. The effects on lipids of pioglitazone are more favourable than those of rosiglitazone. Indeed, pioglitazone appears to be well suited for diabetic dyslipidaemia, increasing high-density lipoprotein (HDL)-cholesterol, decreasing triglycerides and small, dense low-density (LDL) particles with usually no effect on plasma LDL-cholesterol. Rosiglitazone also increases HDL-cholesterol, but has no effect on triglycerides and increases plasma LDL-cholesterol.

Farnier M. · Point Médical, Rond Point de la Nation, 21000 Dijon, France. · Expert Opin Pharmacother. · Pubmed #17563268 No free full text.

Abstract: Mixed hyperlipidaemia is an important risk factor for the development of cardiovascular disease. The global management of mixed hyperlipidaemia is often more difficult than the treatment of pure hypercholesterolaemia in terms of goal attainments. Despite the significant clinical benefits provided by statins, many patients with mixed hyperlipidaemia do not achieve their recommended low-density and non-high-density lipoprotein cholesterol target goals with statin monotherapy. The combination of ezetimibe plus fenofibrate is a new alternative to improve the overall atherogenic lipid profile of patients with mixed hyperlipidaemia. However, the absence of comparative data with statin monotherapy and of long-term clinical studies suggests reservation of the combination of ezetimibe plus fenofibrate as a second-line therapy. Nevertheless, this combination therapy of ezetimibe plus fenofibrate seems particularly useful for patients with a poor response or intolerance to statin monotherapy.

Lambert G. · Université de Nantes, Inserm U539, CHU Hôtel-Dieu, Nantes, France. · Curr Opin Lipidol. · Pubmed #17495605 No free full text.

Abstract: PURPOSE OF REVIEW: Proprotein convertase subtilisin kexin type 9 (PCSK9) has emerged as a potential target for lowering plasma LDL cholesterol levels. This review summarizes recent studies published in print or online before January 2007 which have investigated the functional significance of this intriguing protease. RECENT FINDINGS: Increasing interest in PCSK9 has given rise to landmark epidemiological studies, the generation of animal models, the discovery of new human mutations, as well as numerous in-vitro studies. These studies have helped to unravel the molecular functions of PCSK9. SUMMARY: Mutations of PCSK9 are associated either with hypercholesterolemia or with hypocholesterolemia. In the latter case, the incidence of coronary heart disease is reduced, thereby demonstrating that low LDL cholesterol levels from birth are highly beneficial. PCSK9 promotes the degradation of the LDL receptor in hepatocytes apparently both intracellularly and by being a secreted protein that can bind the LDL receptor and be internalized. By virtue of its role as a major inhibitor of the LDL receptor, PCSK9 is a promising therapeutic target. Specific PCSK9 pharmacological inhibitors may prove to be useful in amplifying the well documented benefits of statins.

Abifadel M, Rabès JP, Boileau C, Varret M. · Inserm, U781, Paris, France. · Ann Endocrinol (Paris). · Pubmed #17391637 No free full text.

Abstract: The genes encoding the low-density lipoproteins receptor and its ligand apolipoprotein B, have been the only two genes classically implicated in autosomal dominant hypercholesterolemia. We have identified in 2003, the third gene implicated in this disease: PCSK9 (Proprotein Convertase Subtilin Kexin 9). Several mutations (p.S127R, p.F216L, p.D374Y...) of this gene have been reported to cause hypercholesterolemia by a gain of function leading to a reduction of LDL receptor levels. Other variations of PCSK9 are conversely associated with hypocholesterolemia particularly the non-sense p.Y142X and p.C679X mutations found in 2% of black Americans and associated with a decrease of LDL levels and coronary heart diseases. PCSK9 substrates and exact role have not been elucidated yet, but it seems that PCSK9 is definitely a major actor in cholesterol homeostasis. PCSK9 inhibitors might constitute new therapeutic targets that would decrease plasma LDL cholesterol levels and be synergistic with statin drugs.

Nitenberg A, Cosson E, Pham I. · Service de Physiologie et d'Explorations Fonctionnelles, Centre Hospitalier Universitaire Jean Verdier, Université Paris 13, Bondy. · Diabetes Metab. · Pubmed #17375404 No free full text.

Abstract: Endothelium plays a key role in the regulation of vascular tone and development of atherosclerosis. Endothelial function is impaired early in patients with risk factors and endothelial dysfunction is a strong and independent predictor of cardiovascular events. Because in normal subjects blood concentrations of glucose, lipids and insulin are increased after each meals, and postprandial changes last a long time after the meals, these changes might be of importance in the process of atherosclerosis initiation and development. Experimental and human studies have shown that a transient increase of blood concentrations of glucose, triglycerides and fatty acids, and insulin are able to depress endothelium-dependent vasodilation in healthy subjects and that hyperglycemia, hypertriglyceridemia and hyperinsulinemia are generator of reactive oxygen species at the origin of a cascade of pathophysiological events resulting in the activation of nuclear factor-kappaB. Nuclear factor-kappaB is an ubiquitous transcription factor controlling the expression of numerous genes and is involved in immunity, inflammation, regulation of cell proliferation and growth and apoptosis. These mechanisms may be involved in the development of atherosclerosis in normal subjects when food intake is chronically modified towards glucids and lipids with cumulative effects both on depression of endothelium dependent dilation and oxidative stress.

El Messal M, Aït Chihab K, Chater R, Loutfi M, Kettani A, Hafidi A, Adlouni A. · Groupe de Génétique et Biologie Moléculaire, Laboratoire de Biochimie, Faculté des Sciences Aïn Chock, Casablanca , Morocco. · Acta Cardiol. · Pubmed #17117756 No free full text.

Abstract: Familial hypercholesterolaemia (FH) is an autosomal dominant disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C) as a result of mutations that impair their removal from plasma.The clinical consequence is a high risk of premature cardiovascular disease. Because of the extreme risk of mortality and morbidity, diagnosis, recruitment and management of FH patients must be one of the priorities of public health. In Morocco, specialized consultation for dyslipidaemia and strategy for management of this cardiovascular major risk factor does not exist, making FH identification and management difficult. In this review, we present the first FH state of the art in our country through a sample of 66 subjects. By this analysis, we have tried to elucidate some points that impede the identification and recruitment of heterozygous FH and the management of both heterozygous and homozygous FH in Morocco. Also, we have attempted to propose some strategies for an adequate management of FH in our country, taking into account the local specifications.

Boursier V. · Service de Médecine Vasculaire, Hôpital Saint-Joseph, Paris. · J Mal Vasc. · Pubmed #17088787 No free full text.

Abstract: Metabolic syndrome is public health problem. The characteristic feature is an association between factors contributing to increased cardiovascular risk. Several definitions have been proposed from 1998 to 2005. All proposed definitions take into consideration insulin resistance and its corollary hyperglycemia, overweight, hypertriglyceridemia, and LDL-cholesterol lowering. The most widely used definitions are proposed by the World Health Organization (WHO) and the American "Cholesterol" program (NCEP-ATpIII). The prevalence of metabolic syndrome varies by geographic region as a function of the chosen definition, the study methodology, the selection criteria, the age and gender of the study population, and the period of the study. Prevalence is higher in the United States than Europe and increases with age. A growing number of adolescents appear to meet the criteria of metabolic syndrome. Irrespective of the definition retained, metabolic syndrome is associated with increased cardiovascular risk and increased risk of type II diabetes. Sound evidence is however lacking on whether the risk is greater than that of taking into account each individual factor. Several points remain to be clarified concerning the underlying mechanisms. Visceral adipose tissue appears to be a key element in the process via anomalous function related to obesity and insulin resistance. Management is based mainly on reduction of body weight and regular physical activity. Drugs may be necessary to correct for the dyslipidemia, normalize blood glucose and reduce blood pressure.

Beaufils M. · Service de Médecine Interne, Hôpital Tenon, Paris. · Presse Med. · Pubmed #16783272 No free full text.

Abstract: Menopause coincides with an increase in the incidence of hypertension in women. A direct role of estrogen deprivation in this increased blood pressure remains a topic of debate. Menopause probably accelerates the arterial changes related to aging. Hormone replacement therapy does not influence blood pressure significantly and is not contraindicated in hypertensive women. The effect of hormone replacement treatment on cardiovascular risk was recently the object of controversy. It does not increase risk except in cases of late treatment in older women who already have atherosclerosis. Hypertension management in women is otherwise similar to management in men.

Bongard V, Ferrières J. · Service d'épidémiologie, CHU de Toulouse, faculté de médecine. · Rev Prat. · Pubmed #16548253 No free full text.

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Fruchart JC, Duriez P. · Lipoprotein and Atherosclerosis Research Unit, INSERM--Unité de Recherche sur l'Arthérosclérose and Lille University 2 U545, Pasteur Institute of Lille, Lille, France. · Drugs Today (Barc). · Pubmed #16511610 No free full text.

Abstract: Epidemiological studies have shown that hypertriglyceridemia and low HDL-cholesterol were both associated with an increased risk of coronary heart disease. Furthermore, hypertriglyceridemia is now recognized as an independent risk factor for coronary artery disease. Secondary prevention trials (e.g., LOCAT, BECAIT, BIP and DAIS) in coronary artery disease with drugs acting primarily on triglycerides (e.g., the PPAR-alpha activators bezafibrate, fenofibrate and gemfibrozil) have shown that reducing triglycerides and increasing HDL-cholesterol, without significantly affecting LDL-cholesterol, slows down coronary artery luminal narrowing. Furthermore, the VA-HIT study recently showed that gemfibrozil decreased coronary artery disease mortality in secondary prevention trials, partly by increasing HDL-cholesterol. The peroxisome proliferator-activated receptors (PPARs) (i.e., PPAR-alpha, -beta(delta) and -gamma) form a subfamily of the nuclear receptor gene family. Whereas all PPARs are, albeit to differing extents, activated by fatty acids and derivatives, PPAR-alpha binds the hypolipidemic fibrates. PPAR-alpha activation mediates changes in lipoprotein metabolism. Moreover, PPAR-alpha activators increase hepatic uptake and esterification of free fatty acids, in addition to increasing mitochondrial free fatty acid uptake and the resulting free fatty acid oxidation. The effect of fibrates on the metabolism of triglyceride-rich lipoproteins is due to a PPAR-alpha-dependent stimulation of lipoprotein lipase and of apolipoprotein (apo)A-V and to an inhibition of apoC-III expression, whereas the increase in plasma HDL-cholesterol depends partly on an overexpression of apoA-I and apoA-II. PPARs are also expressed in atherosclerotic lesions.

Mitchell C, Mallet V, Guidotti JE, Mignon A, Couton D, Kahn A, Gilgenkrantz H. · Institut Cochin, Département de Génétique, Développement et Pathologie Moléculaires, U567 INSERM, CNRS 8101 UMR, Université R. Descartes, 24, rue du Faubourg Saint-Jacques, 75014 Paris, France. · J Soc Biol. · Pubmed #16471264 No free full text.

Abstract: In the liver, the importance of apoptosis is not only evident during development and homeostasis of the biliary tree but plays also a prominent role in liver pathogenesis. Ligand binding to cell surface death receptors such as Fas activates the extrinsic pathway. This pathway predominates in autoimmune liver diseases, viral hepatitis, liver allograft rejection. Hepatocyte apoptosis is also significantly increased in patients with alcoholic hepatitis and nonalcoholic steatohepatitis and correlates with disease severity and hepatic fibrosis. We have used this specific susceptibility of the liver to apoptosis to develop two different approaches: 1) a cell therapy strategy based on a survival advantage to an apoptotic stimulus conferred to transplanted hepatocytes and 2) a new model of hepatocyte conditional ablation based on a controlled activation of the cell death program.

Jakel H, Nowak M, Helleboid-Chapman A, Fruchart-Najib J, Fruchart JC. · Département d'Athérosclérose, UR545 INSERM, Université de Lille II, Loos, France. · Ann Med. · Pubmed #16448983 No free full text.

Abstract: Hypertriglyceridemia is an independent risk factor for the development of cardiovascular disease and is often associated with diabetes, inflammation and the metabolic syndrome. Recently, apolipoprotein A5 (APOA5) was identified as a novel member of the APOA1/C3/A4 gene cluster. Data from mice over-expressing or lacking APOA5 provide direct evidence that this apolipoprotein plays a role in triglyceride metabolism. Moreover, plasma triglyceride levels were found to be strongly associated with APOA5 polymorphisms. The human APOA5 gene is regulated by transcription factors known to affect triglyceride metabolism such as PPARa, RORa, LXR and SREBP-1c and this supports its function. Insulin and interleukins regulate APOA5 gene expression and provide novel clues for the role of this apolipoprotein. To date, the triglyceride lowering action of apoA-V is attributed to the activation of lipoprotein lipase and an acceleration of very low density lipoprotein catabolism. Recent findings indicate that APOA5 could also influence cholesterol homeostasis and probably play a role in hypertriglyceridemia associated with diabetes and inflammation. This review aims to give a comprehensive summary of the current literature and supports the view that APOA5 plays a relevant role in lipid metabolism.

Dufouil C, Alpérovitch A. · INSERM Unité 708, hôpital La Salpêtrière, 75651 Paris. · Rev Prat. · Pubmed #16396227 No free full text.

Abstract: Because of global ageing of the population, the occurrence of Alzheimer's disease (AD) cases is increasing dramatically and AD is becoming a major public health preoccupation. By the year 2020, the World Health Organisation predicts that there will be almost 29 millions demented people throughout the world, two third of them being AD cases. This dramatic perspective could only be modified with new curative treatments or prevention. These last years, there is increasing evidence from epidemiological studies for the role of vascular risk factors in the aetiology of AD among which hypertension, type 2 diabetes, or high cholesterol. These potentially modifiable risk factors raise hope for prevention of Alzheimer's disease.