Role of PCSK9 beyond liver involvement.


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.


Curr Opin Lipidol


Cariou B,Si-Tayeb K,Le May C




Has Abstract


2015-06-01 00:00:00












  • Trials of lipid-lowering therapy in secondary prevention of coronary heart disease.

    abstract::The Scandinavian Simvastatin Survival Study showed that a 35% decrease in LDL-cholesterol was accompanied by a 42% reduction in coronary mortality. Even if the period of time is longer than 1 year for the divergence of survival curves in the simvastatin and placebo groups there are reasons to believe that the benefici...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Olsson AG,Pedersen T,Bergdahl B

    更新日期:1995-12-01 00:00:00

  • Apolipoprotein structural organization in high density lipoproteins: belts, bundles, hinges and hairpins.

    abstract:PURPOSE OF REVIEW:To summarize recent advances towards an understanding of the three-dimensional structures of the apolipoprotein components of HDL with a specific focus on high resolution models of apolipoprotein A-I. RECENT FINDINGS:Since the primary sequence was first reported, various models have been advanced for...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Davidson WS,Silva RA

    更新日期:2005-06-01 00:00:00

  • Molecular genetics of the Smith-Lemli-Opitz syndrome and postsqualene sterol metabolism.

    abstract::The Smith-Lemli-Opitz syndrome is a disorder of morphogenesis resulting from an enzymatic defect in the last step of cholesterol metabolism (reduction of 7-dehydrocholesterol). Analysis of the defective gene and identification of mutations therein have paved the way for the study of the molecular genetics of the disor...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Fitzky BU,Glossmann H,Utermann G,Moebius FF

    更新日期:1999-04-01 00:00:00

  • High density lipoprotein and lipoprotein oxidation.

    abstract::HDL protects LDL from oxidative damage known to contribute to the onset and progression of atherosclerosis. This antioxidant protection by HDL is mediated by intrinsic hydrolytic enzyme systems, by accelerated selective uptake of lipid peroxides from HDL and by antioxidant molecules. Oxidative damage suffered by HDL a...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Banka CL

    更新日期:1996-06-01 00:00:00

  • The role of apolipoprotein A-I-containing lipoproteins in atherosclerosis.

    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


    authors: Forte TM,McCall MR

    更新日期:1994-10-01 00:00:00

  • Impact of rare variants in autosomal dominant hypercholesterolemia causing genes.

    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


    authors: Calandra S,Tarugi P,Bertolini S

    更新日期:2017-06-01 00:00:00

  • Niacin: a long history, but a questionable future.

    abstract:PURPOSE OF REVIEW:To provide an update on recent mechanistic and clinical trial data related to the actions and efficacy of niacin. RECENT FINDINGS:Recent mechanistic studies have provided novel insights regarding the mechanism of action of niacin. Studies of the purported niacin receptor, GPR109A, indicate that niaci...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Ginsberg HN,Reyes-Soffer G

    更新日期:2013-12-01 00:00:00

  • Genetic, biochemical, and clinical features of LCAT deficiency: update for 2020.

    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


    authors: Pavanello C,Calabresi L

    更新日期:2020-08-01 00:00:00

  • Functional food science and food for specified health use policy in Japan: state of the art.

    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


    authors: Arai S,Yasuoka A,Abe K

    更新日期:2008-02-01 00:00:00

  • Unstable coronary plaques and cardiac events in myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits: questions and quandaries.

    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


    authors: Shiomi M,Fan J

    更新日期:2008-12-01 00:00:00

  • Fibrates, dyslipoproteinaemia and cardiovascular disease.

    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


    authors: Watts GF,Dimmitt SB

    更新日期:1999-12-01 00:00:00

  • The paraoxonase gene family and coronary heart disease.

    abstract:PURPOSE OF REVIEW:The antioxidant activity of high-density lipoprotein is largely due to the paraoxonase 1 located on it. Experiments with transgenic paraoxonase 1 knock-out mice indicate the potential for this enzyme to protect against atherogenesis. This effect of high-density lipoprotein in decreasing low-density li...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Mackness B,Durrington PN,Mackness MI

    更新日期:2002-08-01 00:00:00

  • n-3 Fatty acid supplementation and proresolving mediators of inflammation.

    abstract:PURPOSE OF REVIEW:The review presents recent developments in the identification of specialized proresolving mediators (SPMs) of inflammation following supplementation with n-3 fatty acids in humans. RECENT FINDINGS:A number of reports have measured SPMs in human plasma after n-3 fatty acid supplementation. Although st...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Barden AE,Mas E,Mori TA

    更新日期:2016-02-01 00:00:00

  • Recent advances in liver-directed gene therapy: implications for the treatment of dyslipidemia.

    abstract::Somatic gene therapy for the treatment of dyslipidemia is an area of active investigation. A substantial body of data indicates that the transfer of various lipid-lowering genes to the liver is an effective method of restoring normal plasma lipids in animal models of dyslipidemia. Most studies have used adenoviral vec...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Oka K,Davis AR,Chan L

    更新日期:2000-04-01 00:00:00

  • Lowering LDL-cholesterol through diet: potential role in the statin era.

    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


    authors: Bruckert E,Rosenbaum D

    更新日期:2011-02-01 00:00:00

  • Microbiota and HDL metabolism.

    abstract:PURPOSE OF REVIEW:Accumulating evidence has provided new insights regarding potentially effective therapeutic options targeting modulation of HDL metabolism, resulting in the prevention of cardiovascular diseases. The gut microbiota has now been convincingly linked to host health, but its impact on host lipid metabolis...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Nakaya K,Ikewaki K

    更新日期:2018-02-01 00:00:00

  • Exercise and fat accumulation in the human liver.

    abstract:PURPOSE OF REVIEW:Fat accumulation in the liver is strongly associated with metabolic dysfunction. Regular exercise improves many cardiometabolic risks factors; however, its effect on intrahepatic triglyceride (IHTG) content remains elusive. This article summarizes available data regarding the effects of exercise on IH...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Magkos F

    更新日期:2010-12-01 00:00:00

  • Hepatic Niemann-Pick C1-like 1.

    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


    authors: Pramfalk C,Jiang ZY,Parini P

    更新日期:2011-06-01 00:00:00

  • Endocannabinoids and the regulation of their levels in health and disease.

    abstract:PURPOSE OF REVIEW:Endocannabinoids are defined as endogenous agonists of cannabinoid receptors, that is, of the two G-protein-coupled receptors for the Cannabis psychoactive principle Delta-tetra-hydrocannabinol. Two such endogenous mediators have been most thoroughly studied so far: anandamide and 2-arachidonoylglycer...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Di Marzo V,Petrosino S

    更新日期:2007-04-01 00:00:00

  • High-density lipoprotein subclasses.

    abstract::This review describes recent advances that have been made in the separation of HDL subfractions by physicochemical and immunological methods and the relationship between the particles obtained by the different procedures. The metabolic interconversions that occur as a result of cholesteryl ester transfer protein (CETP...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Skinner ER

    更新日期:1994-06-01 00:00:00

  • Epigenetics of paraoxonases.

    abstract:PURPOSE OF REVIEW:Studies have shown the three-member paraoxonase (PON) multigene family to be involved in the development of a large variety of diseases with an inflammatory component. Environmental factors such as lifestyle-related factors differ widely between populations and it is important to consider that their i...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章


    authors: Mahrooz A,Mackness M

    更新日期:2020-08-01 00:00:00

  • Echolucent rupture-prone plaques.

    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


    authors: Nordestgaard BG,Grønholdt ML,Sillesen H

    更新日期:2003-10-01 00:00:00

  • GPIHBP1 and lipolysis: an update.

    abstract:PURPOSE OF REVIEW:This review will provide an update on the structure of GPIHBP1, a 28-kDa glycosylphosphatidylinositol-anchored glycoprotein, and its role in the lipolytic processing of triglyceride-rich lipoproteins. RECENT FINDINGS:Gpihbp1 knockout mice on a chow diet have milky plasma and plasma triglyceride level...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Beigneux AP,Weinstein MM,Davies BS,Gin P,Bensadoun A,Fong LG,Young SG

    更新日期:2009-06-01 00:00:00

  • The paradox of dysfunctional high-density lipoprotein.

    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


    authors: Ansell BJ,Fonarow GC,Fogelman AM

    更新日期:2007-08-01 00:00:00

  • Muscle lipid metabolism in the metabolic syndrome.

    abstract:PURPOSE OF REVIEW:The metabolic syndrome has been emphasized as affecting an important subset of individuals at high risk for cardiovascular disease leading the National Cholesterol Educational Program Adult Treatment Panel III in highlighting awareness of insulin-resistance syndrome. Insulin resistance is thought to b...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Perseghin G

    更新日期:2005-08-01 00:00:00

  • Smooth muscle cell phenotypic switch: implications for foam cell formation.

    abstract:PURPOSE OF REVIEW:It is well accepted that LDLs and its modified form oxidized-LDL (ox-LDL) play a major role in the development of atherosclerosis and foam cell formation. Whereas the majority of these cells have been demonstrated to be derived from macrophages, smooth muscle cells (SMCs) give rise to a significant nu...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Chaabane C,Coen M,Bochaton-Piallat ML

    更新日期:2014-10-01 00:00:00

  • The role of registries and genetic databases in familial hypercholesterolemia.

    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


    authors: Kindt I,Mata P,Knowles JW

    更新日期:2017-04-01 00:00:00

  • Hypertension, dyslipidemia, and insulin resistance: links in a chain or spokes on a wheel?

    abstract::Rather than a link in a causal chain leading to hypertension, insulin resistance and resultant hyperinsulinemia may be 'spokes on a wheel', with central or visceral obesity as the postulated hub of the wheel. Hypertension, hypertriglyceridemia and high density lipoprotein cholesterol are depicted as other spokes. Newl...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Hopkins PN,Hunt SC,Wu LL,Williams GH,Williams RR

    更新日期:1996-08-01 00:00:00

  • Follow-up on primary prevention trials.

    abstract::Recent primary prevention trials demonstrated that cardiovascular morbidity and mortality benefits are not accompanied by adverse effects on overall mortality and morbidity in cohorts representing plasma cholesterol concentrations observed in the bulk of coronary artery disease. During the past year, further analyses ...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Marais AD

    更新日期:1998-12-01 00:00:00

  • Peroxisome proliferator-activated receptors beta/delta: emerging roles for a previously neglected third family member.

    abstract:PURPOSE OF REVIEW:Peroxisome proliferator-activated receptors alpha, beta/delta and gamma are members of the nuclear receptor superfamily. They mediate the effects of fatty acids and their derivatives at the transcriptional level, and are considered to be lipid sensors that participate in the regulation of energy homeo...

    journal_title:Current opinion in lipidology

    pub_type: 杂志文章,评审


    authors: Michalik L,Desvergne B,Wahli W

    更新日期:2003-04-01 00:00:00