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:A healthy diet should be rich in vegetables and fruits, whole-grain, high-fiber foods, and fish and should contain a small amount of saturated and trans fats. In addition to these recommendations, some food ingredients such as plant sterol/stanol soy protein and isoflavones may help reduce cholesterol...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e328340b8e7
更新日期:2011-02-01 00:00:00
abstract::Atherosclerotic cardiovascular disease is the most common complication of diabetes. Recent guidelines in the USA have underlined the importance of treating lipid abnormalities in people with diabetes in order to reduce the risk of this complication. Should lifestyle approaches not be sufficient drugs will need to be a...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-200112000-00003
更新日期:2001-12-01 00:00:00
abstract::The microsomal triglyceride transfer protein is necessary for the assembly and secretion of lipoproteins containing apolipoprotein B. During the past year, significant progress has been made towards understanding the role of microsomal triglyceride transfer protein in lipoprotein assembly at both a cellular and molecu...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-199706000-00002
更新日期:1997-06-01 00:00:00
abstract::Most of the LDL receptor family members recognize apolipoprotein E. The structures of the VLDL receptor, and recently identified apolipoprotein E receptor 2, closely resemble the LDL receptor. Recent studies have demonstrated that the VLDL receptor is responsible for the reproduction of premammalian species by mediati...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-199610000-00007
更新日期:1996-10-01 00:00:00
abstract:PURPOSE OF REVIEW:Cardiovascular risk scoring is incorporated in guidelines and recommended for targeting preventive treatment. Evidence is required on the most appropriate method, its accuracy in a given population, and its effectiveness in favourably influencing clinical behaviour and health outcomes. RECENT FINDING...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/01.mol.0000236362.56216.44
更新日期:2006-08-01 00:00:00
abstract:PURPOSE OF REVIEW:Use of suitable animal models is essential for investigation of the mechanisms underlying cardiac events and development of the therapeutic strategies; however, ideal animal models that can recapitulate human coronary atherosclerosis and subsequent acute myocardial infarction are still lacking. In thi...
journal_title:Current opinion in lipidology
pub_type: 社论,评审
doi:10.1097/MOL.0b013e3283189c18
更新日期:2008-12-01 00:00:00
abstract:PURPOSE OF REVIEW:To assess factors that promote atherogenesis and cardiovascular disease (CVD) in rheumatoid arthritis (RA). Also, to determine how control of inflammation with conventional and biological antirheumatic drugs affects cardiovascular risk. RECENT FINDINGS:An excess risk of CVD occurs early in the RA dis...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e3283488c50
更新日期:2011-08-01 00:00:00
abstract::Expression profiling and genomic DNA sequence comparisons are increasingly being applied to the identification and analysis of the genes that are involved in lipid metabolism. Not only has genome-wide expression profiling aided in the identification of novel genes that are involved in important processes in lipid meta...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-200204000-00009
更新日期:2002-04-01 00:00:00
abstract:PURPOSE OF REVIEW:Nonalcoholic fatty liver (NAFL) and especially its inflammatory variant nonalcoholic steatohepatitis (NASH) have become a major challenge to healthcare systems worldwide because of the increasing prevalence of its major risk factors obesity and type 2 diabetes, which are closely linked to overeating, ...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e32834c7cfc
更新日期:2011-12-01 00:00:00
abstract::PURPOSE OF REVIEW This review discusses recent progress in the role of ATP-binding cassette proteins ABCG5 and G8 in dietary sterol absorption, excretion and pathogenesis of cardiovascular disease. RECENT FINDINGS Identification of the genetic defect(s) underlying sitosterolemia has led to a renewed interest in the me...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/01.mol.0000083763.66245.18
更新日期:2003-08-01 00:00:00
abstract:PURPOSE OF REVIEW:Routine measurement of echolucency of atherosclerotic plaques, in addition to degree of stenosis, may change clinical practice in the future. Within the context of previous knowledge in this field, we therefore review recent developments in detection and histological characterization of echolucent rup...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/01.mol.0000092628.86399.9f
更新日期:2003-10-01 00:00:00
abstract:PURPOSE OF REVIEW:Dyslipidaemias are a major risk factor for cardiovascular disease (CVD); in particular, high levels of low-density lipoprotein cholesterol (LDL-C) have been associated to a higher cardiovascular risk. Reducing LDL-C levels decreases the risk of coronary heart disease (CHD), and the greater the LDL-C r...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000459
更新日期:2017-12-01 00:00:00
abstract:PURPOSE OF REVIEW:The discovery of Niemann-Pick C1-like 1 (NPC1L1) and ezetimibe, a drug that lowers intestinal cholesterol absorption, has contributed to the recognition of the intestine as an important organ in whole-body cholesterol homeostasis. Unfortunately, the majority of the studies on NPC1L1 have been conducte...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e3283468c28
更新日期:2011-06-01 00:00:00
abstract:PURPOSE OF REVIEW:To summarize the recent studies directly comparing LDL and lipoprotein(a) as causal factors for cardiovascular disease and mortality. RECENT FINDINGS:In approximately 100,000 individuals from the Copenhagen General Population Study for risk of myocardial infarction, in observational analyses per 39 m...
journal_title:Current opinion in lipidology
pub_type: 杂志文章
doi:10.1097/MOL.0000000000000681
更新日期:2020-06-01 00:00:00
abstract:PURPOSE OF REVIEW:To review how leveraging familial hypercholesterolemia registries can impact molecular genetic research and precision medicine. RECENT FINDINGS:Familial hypercholesterolemia is both much more common and more phenotypically heterogeneous than previously thought with some evidence for significant genot...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000398
更新日期:2017-04-01 00:00:00
abstract:PURPOSE OF REVIEW:The new risk-based guidelines on blood cholesterol treatment from the American College of Cardiology and the American Heart Association reflect the now widespread international agreement that lipid-lowering treatment decisions should be based primarily on individuals' predicted cardiovascular disease ...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000089
更新日期:2014-08-01 00:00:00
abstract::The plasminogen and coagulation systems have been extensively characterized at the biochemical level. Recent gene targeting and gene transfer studies have provided novel insights into their role in the formation of blood vessels and in the pathogenesis of blood vessel disorders including thrombosis, restenosis and ath...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-199704000-00010
更新日期:1997-04-01 00:00:00
abstract:PURPOSE OF REVIEW:The effects of hormone-replacement therapy on cardiovascular risk factors are examined. In an attempt to explain the results of recent randomized controlled trials in which no benefit of hormone-replacement therapy for postmenopausal women has been observed, RECENT FINDINGS:Changes in lipoproteins in...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/01.mol.0000137231.84772.80
更新日期:2004-08-01 00:00:00
abstract:PURPOSE OF REVIEW:Lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease; we highlight the most recent research initiatives that have sought to define Lp(a)-dependent pathogenicity as well as pharmacologic approaches to lowering Lp(a). RECENT FINDINGS:Recent large-scale meta-analyses have confirmed elevate...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e32835111d8
更新日期:2012-04-01 00:00:00
abstract:PURPOSE OF REVIEW:Hepatic steatosis is a leading cause of adult and paediatric liver disease and is inextricably linked to obesity, insulin resistance and cardiovascular disease. Here we summarize our current understanding of the role of the patatin-like phospholipase domain-containing 3 gene (PNPLA3) in hepatic steato...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/mol.0b013e328338ca61
更新日期:2010-06-01 00:00:00
abstract::The VLDL receptor (VLDLR) is a member of the LDL receptor family. The VLDLR was hypothesized to mediate fatty acid entry into peripheral tissues, on the basis of its expression in tissues that are active in fatty acid metabolism and its capacity to bind apolipoprotein-E-rich VLDL in vitro. This hypothesis initially pr...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-200106000-00006
更新日期:2001-06-01 00:00:00
abstract::Thia substituted fatty acids are saturated fatty acids which are modified by insertion of a sulfur atom at specific positions in the carbon backbone. During the last few years pleiotropic effects of the 3-thia fatty acid tetradecylthioacetic acid have been revealed. The biological responses to tetradecylthioacetic aci...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-200206000-00010
更新日期:2002-06-01 00:00:00
abstract:PURPOSE OF REVIEW:To examine the role of gut microbiota in the regulation of host energy homeostasis and its role in the pathogenesis of obesity, diabetes and nonalcoholic fatty liver disease (NAFLD). RECENT FINDINGS:Experimental models highlight several mechanisms connecting gut microbiota to host energy metabolism: ...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e3283347ebb
更新日期:2010-02-01 00:00:00
abstract:PURPOSE OF REVIEW:Hypoxia triggers various cellular processes, both in physiological and pathological conditions, and has recently also been implicated in atherosclerosis. This review summarizes the recent evidence for the presence and the role of hypoxia in atherosclerosis. Additionally, it will elucidate on hypoxic s...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e32836484a4
更新日期:2013-10-01 00:00:00
abstract:PURPOSE OF REVIEW:In recent years, many of the concerns surrounding the glycemic index have been addressed by methodological studies and clinical trials comparing diets carefully matched for other nutrients. These findings are reviewed together with new observational evidence for the role of the dietary glycemic index ...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e32834ec705
更新日期:2012-02-01 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:PURPOSE OF REVIEW:The purpose of this review is to present recent information on lipid lowering in diabetes mellitus. New information from randomized clinical trials will be discussed together with implications for clinical practice. Residual risk persists despite statin therapy and additional approaches, particularly ...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0b013e328314b6b4
更新日期:2008-12-01 00:00:00
abstract:PURPOSE OF REVIEW:The article reviews the challenges facing cardiovascular disease (CVD) guidelines committees. RECENT FINDINGS:Clinical trials in high-risk populations have shown additional CVD event reduction with ezetimibe and proprotein convertase subtilisin-kexin-9 inhibitors. These trials recruit middle-aged sec...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/MOL.0000000000000453
更新日期:2017-12-01 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::The inhibiting effect of insulin on the mobilization of free fatty acids (FFA) from adipose tissue is halted in prevalent conditions with systemic insulin resistance. The nature and cause of this perturbation are unknown, but steroid hormones may be involved. The consequence is the creation or amplification of insulin...
journal_title:Current opinion in lipidology
pub_type: 杂志文章,评审
doi:10.1097/00041433-199405030-00003
更新日期:1994-06-01 00:00:00