Abstract:
PURPOSE OF REVIEW:Proprotein convertase subtilisin kexin type 9 (PCSK9) acts as an endogenous natural inhibitor of the LDL receptor pathway, by targeting the receptor to lysosomes for degradation. Beside the liver, PCSK9 is also expressed at significant levels in other tissues, where its function remains unclear. The current review focuses on the extrahepatic actions of PCSK9. RECENT FINDINGS:The generation of liver-specific PCSK9 knockout mice has clearly indicated that PCSK9 affects cholesterol homeostasis via its action on extrahepatic organs. PCSK9 is highly expressed in the intestine, where it controls the production of triglyceride-rich lipoproteins and the transintestinal cholesterol excretion. The role of PCSK9 in the endocrine pancreas and glucose homeostasis remains unclear because conflicting data exist concerning the metabolic phenotype of PCSK9-deficient mice. Sparse data suggest that PCSK9 might also play a role in kidneys, vascular smooth muscle cells, and neurons. SUMMARY:Based on the virtuous combination of genetic and pharmacological approaches, the major function of PCSK9 as a key regulator of hepatic LDL receptor metabolism had quickly emerged. Accumulating evidence indicates that intestinal PCSK9 is also involved in the modulation of lipid homeostasis. Additional studies are warranted to decipher the physiological function of PCSK9 in other extrahepatic tissues and thus to better assess the safety of PCSK9 inhibitors.
journal_name
Curr Opin Lipidoljournal_title
Current opinion in lipidologyauthors
Cariou B,Si-Tayeb K,Le May Cdoi
10.1097/MOL.0000000000000180subject
Has Abstractpub_date
2015-06-01 00:00:00pages
155-61issue
3eissn
0957-9672issn
1473-6535journal_volume
26pub_type
杂志文章,评审abstract:PURPOSE OF REVIEW:Familial hypercholesterolemia is associated with a high lifetime risk of atherosclerotic cardiovascular disease (ASCVD). However, this risk is variable. This review evaluates recent evidence related to ASCVD risk stratification in familial hypercholesterolemia considering aspects of phenotype and geno...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000391
更新日期:2017-04-01 00:00:00
abstract:PURPOSE OF REVIEW:The aim of this review is to present the latest findings on the role of the circadian clock in the control of metabolism, and the therapeutic potential of chronotherapy to regulate energy homeostasis in humans. RECENT FINDINGS:We summarized the recent advances related to circadian clock regulation of...
journal_title:Current opinion in lipidology
pub_type: 杂志文章
doi:10.1097/MOL.0000000000000722
更新日期:2021-02-01 00:00:00
abstract::The development of atherosclerosis in animal models and the incidence of coronary heart disease in postmenopausal women are markedly reduced by estrogen treatment. Estrogen have acute beneficial effects on vascular reactivity and longer-term effects on critical steps in the pathogenesis of atherosclerosis. Phytoestrog...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-199810000-00010
更新日期:1998-10-01 00:00:00
abstract::Based on evidence that hormone replacement therapy is cardioprotective, enthusiasm for universal hormone replacement therapy in postmenopausal women has grown Estrogens lower LDL, raise HDL, dilate arteries and reduce LDL oxidation potential. However, the benefits of hormone replacement therapy must be weighed against...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-199612000-00005
更新日期:1996-12-01 00:00:00
abstract:PURPOSE OF REVIEW:Homozygous familial hypercholesterolemia (HoFH) is a rare disorder associated with early atherosclerotic disease due to impairment of the LDL receptor (LDLR) pathway. Because of their molecular defect, current treatment options have limited success in bringing HoFH patient to LDL-C target and morbidit...
journal_title:Current opinion in lipidology
pub_type: 杂志文章
doi:10.1097/MOL.0000000000000677
更新日期:2020-06-01 00:00:00
abstract:PURPOSE OF REVIEW:Adipose tissue is an essential, highly dynamic and metabolically active tissue that vigorously communicates to support its primary function: the storage of lipids. It performs this function to secure energy supply and prevent lipotoxicity. Adipose tissue is essential for maintaining a healthy glucose ...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e3282f39f95
更新日期:2008-02-01 00:00:00
abstract::Further understanding of the causative link between plasma lipids and coronary heart disease will come from a deeper appreciation of the impact of lipoprotein heterogeneity on the processes of atherosclerosis and thrombosis. It is now widely appreciated that remnants of triglyceride-rich lipoproteins, IDL and specific...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-199906000-00006
更新日期:1999-06-01 00:00:00
abstract:PURPOSE OF REVIEW:The systematic analysis of the major candidate genes in autosomal dominant hypercholesterolemia (ADH) and the use of next-generation sequencing (NGS) technology have made possible the discovery of several rare gene variants whose pathogenic effect in most cases remains poorly defined. RECENT FINDINGS...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000414
更新日期:2017-06-01 00:00:00
abstract:PURPOSE OF REVIEW:It is well recognized that adipose tissue in obesity is characterized by macrophage accumulation and local inflammation. This review summarizes current evidence regarding dietary cholesterol on adipose tissue macrophage accrual, systemic inflammation and its potential link to atherosclerosis. RECENT ...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/mol.0b013e32831bef8b
更新日期:2009-02-01 00:00:00
abstract:PURPOSE OF REVIEW:The current review considers what we have learnt from the clinical outcome trials with the cetrapibs; the inhibitors of cholesteryl ester transfer protein that increase HDL cholesterol levels; torcetrapib, dalcetrapib, evacetrapib and anacetrapib. RECENT FINDINGS:Although an off-target increase in bl...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000518
更新日期:2018-08-01 00:00:00
abstract:PURPOSE OF REVIEW:Brown adipose tissue (BAT) is an emerging target to combat cardiometabolic disorders as it can take up substantial amounts of glucose and lipids from the circulation for heat production. This review focuses on new concepts in BAT physiology and discusses the need for new techniques to determine BAT ac...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000296
更新日期:2016-06-01 00:00:00
abstract:PURPOSE OF REVIEW:Control of vascular smooth muscle cell (VSMC) phenotype is essential in the development and maintenance of a healthy vasculature. Acquisition of a synthetic, proproliferative phenotype by VSMCs following vascular insult is central to neointimal formation and the development of vascular pathology. Micr...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e32835719a1
更新日期:2012-10-01 00:00:00
abstract::The menopause and its biology are as yet still incompletely understood. Very little is known about biological and molecular changes in cardiovascular target tissues and organs after menopause. Experimental and clinical evidence indicate that prevention of cardiovascular disease by estrogens is aimed both at the correc...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-199708000-00007
更新日期:1997-08-01 00:00:00
abstract:PURPOSE OF REVIEW:It is increasingly recognized that profound metabolic changes occur in activated myeloid cells, which shape their inflammatory phenotype and cellular functions. The purpose of this review is to summarize the accumulating evidence that major metabolic adaptations occur in monocytes and macrophages in t...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000539
更新日期:2018-10-01 00:00:00
abstract:PURPOSE OF REVIEW:This review addresses how, in atherosclerosis or systemic inflammation, HDL can lose its usual atheroprotective characteristics and even paradoxically assume proinflammatory properties. RECENT FINDINGS:Specific chemical and structural changes within HDL particles can impede reverse cholesterol transp...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e3282364a17
更新日期:2007-08-01 00:00:00
abstract:PURPOSE OF REVIEW:The 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors, or statins, have been shown to reduce cardiovascular morbidity and mortality among a wide spectrum of patients with established atherosclerotic vascular disease. Mounting experimental and clinical evidence also suggest a potential benefit...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/01.mol.0000191916.89121.d3
更新日期:2005-12-01 00:00:00
abstract::Recent epidemiological data have reaffirmed that elevated plasma triglyceride and low HDL-cholesterol levels are important risk factors for atherosclerotic vascular disease. The rationale for the clinical use of fibric acid derivatives, which are designed to correct this metabolic nexus, is now on firmer ground. The m...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-199912000-00011
更新日期:1999-12-01 00:00:00
abstract:PURPOSE OF REVIEW:The endoplasmic reticulum (ER) maintains cellular metabolic homeostasis by coordinating protein synthesis, secretion activities, lipid biosynthesis and calcium (Ca²⁺) storage. In this review, we will discuss how altered ER homeostasis contributes to dysregulation of hepatic lipid metabolism and contri...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000056
更新日期:2014-04-01 00:00:00
abstract::The present review summarizes recent advances in the transcriptional regulation of the human apolipoprotein genes, focusing mostly, but not exclusively, on in-vivo studies and signaling mechanisms that affect apolipoprotein gene transcription. An attempt is made to explain how interactions of transcription factors tha...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-200104000-00012
更新日期:2001-04-01 00:00:00
abstract::The most likely cholesterol-raising factors in unfiltered coffee are kahweol and cafestol. Different brewing methods alter the concentrations of these diterpenes and have caused discrepant results in studies from different parts of the world. The effect of tea on the risk of coronary heart disease is much less clear b...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-199502000-00006
更新日期:1995-02-01 00:00:00
abstract::The inverse relationship between HDL and apolipoprotein A-I concentrations and the risk for premature atherosclerosis is well established, but the mechanism whereby apolipoprotein A-I offers protection is still somewhat elusive. Recent studies suggest that a specific subpopulation within the lipoprotein (AI) subclass ...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-199410000-00007
更新日期:1994-10-01 00:00:00
abstract:PURPOSE OF REVIEW:HDLs possess several physiological activities that may explain their antiatherosclerotic properties. Among them, the most relevant is the ability of HDL to promote the efflux of excess cholesterol from peripheral tissues to the liver for excretion. RECENT FINDINGS:The ability of HDL to promote choles...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e32834adac3
更新日期:2011-10-01 00:00:00
abstract:PURPOSE OF REVIEW:The science and policy of functional foods are a matter of global concern and this review provides up-to-date information about the Japanese 'food for specified health use' policy based on functional food science. RECENT FINDINGS:A great many studies on nonnutritive but physiologically functional foo...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e3282f3f505
更新日期:2008-02-01 00:00:00
abstract:PURPOSE OF REVIEW:The fish fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may promote cardiometabolic health. This review summarizes the results of recent meta-analyses of prospective studies on cardiovascular diseases, diabetes type 2 and markers of atherosclerosis and thrombosis. RECENT FINDI...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000041
更新日期:2014-02-01 00:00:00
abstract:PURPOSE OF REVIEW:Atherosclerosis is a chronic inflammatory disease in which subendothelial infiltration of lipoproteins leads to inflamed lesions in arteries. Despite improvements in secondary prevention, most cardiovascular events cannot be avoided with current therapies. This review focuses on novel mechanistic insi...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000540
更新日期:2018-10-01 00:00:00
abstract:PURPOSE OF REVIEW:Fibrates continue to be a viable treatment option for mixed atherogenic dyslipidemia, and recent reports from clinical studies have shed new light on the therapeutic utility of fibrates for the prevention of microvascular and macrovascular disease, especially in combination with statins. RECENT FINDI...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e32834701c3
更新日期:2011-08-01 00:00:00
abstract:PURPOSE OF REVIEW:Dementia is a major cause of disability and institutionalization. Apart from age and apolipoprotein E (APOE) genotype, there are currently no established, clinically relevant, noninvasive markers of dementia. We conducted a literature search of recent observational epidemiological studies evaluating t...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000257
更新日期:2016-02-01 00:00:00
abstract:PURPOSE OF REVIEW:To provide an update on clinical trials of gene therapy for atherosclerotic cardiovascular disease published since 1 August 2001 and summarize the general advantages and potential problems of gene transfer in these disorders. RECENT FINDINGS:There are two major areas in which gene therapy has entered...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-200212000-00009
更新日期:2002-12-01 00:00:00
abstract:PURPOSE OF REVIEW:This review covers recent developments in microarray studies in the field of atherogenesis research. RECENT FINDINGS:During the past year microarrays have been applied to the analysis of pathogenic mechanisms of several atherosclerosis risk factors, including ageing, hypertension, obesity, and cytome...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/01.mol.0000162325.85290.e5
更新日期:2005-04-01 00:00:00
abstract:PURPOSE OF REVIEW:Genetic LCAT deficiency is a rare metabolic disorder characterized by low-plasma HDL cholesterol levels. Clinical manifestations of the disease include corneal opacification, anemia, and renal disease, which represents the major cause of morbidity and mortality in carriers. RECENT FINDINGS:Biochemica...
journal_title:Current opinion in lipidology
pub_type: 杂志文章
doi:10.1097/MOL.0000000000000697
更新日期:2020-08-01 00:00:00