Current opinion in lipidology最新文献_第4页

ANGPTL3 and ApoC-III inhibitors for treating hypertriglyceridemia in context: horses for courses? 用于治疗高甘油三酯血症的 ANGPTL3 和 ApoC-III 抑制剂的背景：马到成功？

IF 4.4 3区医学

Current opinion in lipidology Pub Date : 2024-06-01 Epub Date: 2024-02-19 DOI: 10.1097/MOL.0000000000000920

Dick C Chan, Gerald F Watts

{"title":"ANGPTL3 and ApoC-III inhibitors for treating hypertriglyceridemia in context: horses for courses?","authors":"Dick C Chan, Gerald F Watts","doi":"10.1097/MOL.0000000000000920","DOIUrl":"10.1097/MOL.0000000000000920","url":null,"abstract":"Purpose of review: Hypertriglyceridemia (HTG) is an independent and casual risk factor for atherosclerotic cardiovascular disease (ASCVD). There is an unmet need for more effective treatments for patients with HTG. Angiopoietin-like protein 3 (ANGPTL3) and apolipoprotein C-III (apoC-III) are key regulators of triglyceride-rich lipoprotein (TRL) metabolism. We review recent clinical trials targeting ANGPTL3 and apoC-III with monoclonal antibody and nucleic acid therapies, including antisense oligonucleotides and small interfering RNA.Recent findings: ANGPTL3 and apoC-III inhibitors are effective in lowering plasma triglycerides and TRLs, with possibly greater efficacy with the inhibition of apoC-III. By contrast to ANGPTL3 inhibition that has the advantage of greater lowering of plasma low-density lipoprotein (LDL)-cholesterol and apoB levels, apoC-III inhibition only has a modest or no effect in lowering plasma LDL-cholesterol and apoB concentrations. Therapeutic inhibition of ANGPTL3 and apoC-III can correct HTG possibly by reducing production and increasing catabolism of TRL particles, but this remains to be formally investigated in patients with HTG.Summary: Novel agents targeting ANGPTL3 and apoC-III can correct HTG and potentially lower risk of ASCVD in patients with HTG. The long-term safety and cost-effectiveness of these agents await confirmation in ongoing and future studies.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"101-109"},"PeriodicalIF":4.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Remnant cholesterol as a new lipid-lowering target to reduce cardiovascular events. 残余胆固醇是减少心血管事件的新降脂目标。

IF 4.4 3区医学

Current opinion in lipidology Pub Date : 2024-06-01 Epub Date: 2024-01-23 DOI: 10.1097/MOL.0000000000000921

Paolo Raggi, Maria Laura Becciu, Eliano P Navarese

引用次数: 0

PCSK9-directed therapies: an update. PCSK9导向疗法：最新进展。

IF 4.4 3区医学

Current opinion in lipidology Pub Date : 2024-06-01 Epub Date: 2024-01-19 DOI: 10.1097/MOL.0000000000000919

Julius L Katzmann, Ulrich Laufs

{"title":"PCSK9-directed therapies: an update.","authors":"Julius L Katzmann, Ulrich Laufs","doi":"10.1097/MOL.0000000000000919","DOIUrl":"10.1097/MOL.0000000000000919","url":null,"abstract":"Purpose of review: Two large cardiovascular outcomes trials of monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) demonstrated that therapeutic inhibition of extracellular PCSK9 markedly reduces LDL cholesterol concentration and cardiovascular risk. Several novel strategies to inhibit PCSK9 function are in development. Different mechanisms of action may determine specific properties with potential relevance for patient care.Recent findings: For the monoclonal antibodies evolocumab und alirocumab as first-generation PCSK9 inhibitors, follow-up data of up to 8 years of exposure complement the information on efficacy and safety available from outcome trials. For the small-interfering RNA inclisiran as second-generation PCSK9 inhibitor, several phase III trials have been published and a cardiovascular outcome trial has completed recruitment and is ongoing. Third-generation PCSK9 inhibitors encompass, among others, orally available drugs such as MK-0616 and the fusion protein lerodalcibep. Additional strategies to inhibit PCSK9 include vaccination and gene editing.Summary: Long-term inhibition of PCSK9 with monoclonal antibodies is safe and conveys sustained cardiovascular benefit. Novel strategies to inhibit PCSK9 function such as orally available drugs, RNA targeting, and one-time treatment with gene editing may further enhance the therapeutic armamentarium and enable novel preventive strategies.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"117-125"},"PeriodicalIF":4.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139566546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Newborn screening for lipid disorders. 新生儿血脂紊乱筛查。

IF 4.4 3区医学

Current opinion in lipidology Pub Date : 2024-06-01 Epub Date: 2024-02-26 DOI: 10.1097/MOL.0000000000000928

Xiangqiang Shao, Robert Steiner, Amy L Peterson

{"title":"Newborn screening for lipid disorders.","authors":"Xiangqiang Shao, Robert Steiner, Amy L Peterson","doi":"10.1097/MOL.0000000000000928","DOIUrl":"10.1097/MOL.0000000000000928","url":null,"abstract":"Purpose of review: Newborn screening is one of the most successful public health programs of the last century and offers unparalleled access to universal screening for a variety of metabolic and other disorders. Interest in development of newborn screening for lipid disorders has intensified in recent years. Screening newborns for lipid disorders has important implications for the health of the newborn as well as their relatives, and in the case of more common lipid disorders like familial hypercholesterolemia, could have important public health implications.Recent findings: Recent studies have demonstrated feasibility of measuring biomarkers for heterozygous familial hypercholesterolemia from newborn screening dried blood spot specimens. Another lipid disorder, cerebrotendinous xanthomatosis, is currently amenable to newborn screening utilizing currently available assays. New research in next-generation sequencing as a primary screen in newborns will also identify both common and rare lipid disorders in newborns.Summary: Historically, newborn screening for lipid disorders was not done for many reasons, but new research has developed testing methods that may successfully identify common and rare lipid disorders. This will impact the health of the newborn but could also impact family members and public health.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"149-156"},"PeriodicalIF":4.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

G protein-coupled receptor 146: new insights from genetics and model systems. G 蛋白偶联受体 146：遗传学和模型系统的新见解。

IF 4.4 3区医学

Current opinion in lipidology Pub Date : 2024-06-01 Epub Date: 2024-03-08 DOI: 10.1097/MOL.0000000000000929

Umesh Tharehalli, Antoine Rimbert

{"title":"G protein-coupled receptor 146: new insights from genetics and model systems.","authors":"Umesh Tharehalli, Antoine Rimbert","doi":"10.1097/MOL.0000000000000929","DOIUrl":"10.1097/MOL.0000000000000929","url":null,"abstract":"Purpose of review: Atherosclerotic cardiovascular diseases continue to be a significant global cause of death. Despite the availability of efficient treatments, there is an ongoing need for innovative strategies to lower lipid levels, especially for individuals experiencing refractory dyslipidemias or intolerable adverse effects. Based on human genetic findings and on mouse studies, the G protein-coupled receptor 146 (GPR146) emerges as a promising target against hypercholesterolemia and atherosclerosis. The present review aims at providing a thorough summary of the latest information acquired regarding GPR146, encompassing genetic evidence, functional insights, and its broader implications for cardiometabolic health.Recent findings: Human genetic studies uncovered associations between GPR146 variants, plasma lipid levels and metabolic parameters. Additionally, GPR146's influence extends beyond lipid regulation, impacting adipocyte differentiation, lipolysis, and inflammation pathways. Despite GPR146's orphan status, ongoing efforts to deorphanize it, suggest a potential ligand with downstream effects involving Gαi coupling.Summary: Here, we outline and deliberate on recent progress focused on: enhancing comprehension of the effects of inhibiting GPR146 in humans through genetic instruments, evaluating the extra-hepatic functions of GPR146, and discovering its natural ligand(s). Grasping these biological parameters and mechanisms is crucial in the exploration of GPR146 as a prospective therapeutic target.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"162-169"},"PeriodicalIF":4.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

C-reactive protein, pharmacological treatments and diet: how to target your inflammatory burden. C反应蛋白、药物治疗和饮食：如何减轻炎症负担。

IF 4.4 3区医学

Current opinion in lipidology Pub Date : 2024-06-01 Epub Date: 2024-01-25 DOI: 10.1097/MOL.0000000000000922

Benjamin Bay, Natalie Arnold, Christoph Waldeyer

{"title":"C-reactive protein, pharmacological treatments and diet: how to target your inflammatory burden.","authors":"Benjamin Bay, Natalie Arnold, Christoph Waldeyer","doi":"10.1097/MOL.0000000000000922","DOIUrl":"10.1097/MOL.0000000000000922","url":null,"abstract":"Purpose of review: This article focuses on pharmacological agents as well as dietary changes aimed at the reduction of the inflammatory burden measured by circulating C-reactive protein concentrations.Recent findings: Over the last years, repurposed as well as new anti-inflammatory agents have been investigated in outcome trials in the cardiovascular field. Currently, a specific inhibition of the inflammatory cascade via the interleukin-6 ligand antibody ziltivekimab is being explored in large-scale outcome trials, after the efficacy of this agent with regard to the reduction of inflammatory biomarkers was proven recently. Next to the investigated pharmacological agents, specific dietary patterns possess the ability to improve the inflammatory burden. This enables patients themselves to unlock a potential health benefit ahead of the initiation of a specific medication targeting the inflammatory pathway.Summary: Both pharmacological agents as well as diet provide the opportunity to improve the inflammatory profile and thereby lower C-reactive protein concentrations. Whilst advances in the field of specific anti-inflammatory treatments have been made over the last years, their broad implementation is currently limited. Therefore, optimization of diet (and other lifestyle factors) could provide a cost effective and side-effect free intervention to target low-grade vascular inflammation.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"141-148"},"PeriodicalIF":4.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139562580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lipid metabolism during pregnancy: consequences for mother and child. 孕期脂质代谢：对母婴的影响。

IF 4.4 3区医学

Current opinion in lipidology Pub Date : 2024-06-01 Epub Date: 2024-02-21 DOI: 10.1097/MOL.0000000000000927

Janneke W C M Mulder, D Meeike Kusters, Jeanine E Roeters van Lennep, Barbara A Hutten

{"title":"Lipid metabolism during pregnancy: consequences for mother and child.","authors":"Janneke W C M Mulder, D Meeike Kusters, Jeanine E Roeters van Lennep, Barbara A Hutten","doi":"10.1097/MOL.0000000000000927","DOIUrl":"10.1097/MOL.0000000000000927","url":null,"abstract":"Purpose of review: Accommodating fetal growth and development, women undergo multiple physiological changes during pregnancy. In recent years, several studies contributed to the accumulating evidence about the impact of gestational hyperlipidemia on cardiovascular risk for mother and child. This review aims to provide a comprehensive overview of the current research on lipid profile alterations during pregnancy and its associated (cardiovascular) outcomes for mother and child from a clinical perspective.Recent findings: In a normal pregnancy, total and LDL-cholesterol levels increase by approximately 30-50%, HDL-cholesterol by 20-40%, and triglycerides by 50-100%. In some women, for example, with familial hypercholesterolemia (FH), a more atherogenic lipid profile is observed. Dyslipidemia during pregnancy is found to be associated with adverse (cardiovascular) outcomes for the mother (e.g. preeclampsia, gestational diabetes, metabolic syndrome, unfavorable lipid profile) and for the child (e.g. preterm birth, large for gestational age, preatherosclerotic lesions, unfavorable lipid profile).Summary: The lipid profile of women during pregnancy provides a unique window of opportunity into the potential future cardiovascular risk for mother and child. Better knowledge about adverse outcomes and specific risk groups could lead to better risk assessment and earlier cardiovascular prevention. Future research should investigate implementation of gestational screening possibilities.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"133-140"},"PeriodicalIF":4.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11064913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Familial hypercholesterolemia in children and the importance of early treatment. 儿童家族性高胆固醇血症和早期治疗的重要性。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-06-01 Epub Date: 2024-02-14 DOI: 10.1097/MOL.0000000000000926

Sibbeliene E van den Bosch, Barbara A Hutten, Willemijn E Corpeleijn, D Meeike Kusters

引用次数: 0

Basic and translational evidence supporting the role of TM6SF2 in VLDL metabolism. 支持 TM6SF2 在 VLDL 代谢中发挥作用的基础和转化证据。

IF 4.4 3区医学

Current opinion in lipidology Pub Date : 2024-06-01 Epub Date: 2024-03-08 DOI: 10.1097/MOL.0000000000000930

Jing Liu, Henry N Ginsberg, Gissette Reyes-Soffer

{"title":"Basic and translational evidence supporting the role of TM6SF2 in VLDL metabolism.","authors":"Jing Liu, Henry N Ginsberg, Gissette Reyes-Soffer","doi":"10.1097/MOL.0000000000000930","DOIUrl":"10.1097/MOL.0000000000000930","url":null,"abstract":"Purpose of review: Transmembrane 6 superfamily member 2 ( TM6SF2 ) gene was identified through exome-wide studies in 2014. A genetic variant from glutamic acid to lysine substitution at amino acid position 167 (NM_001001524.3:c.499G> A) (p.Gln167Lys/p.E167K, rs58542926) was discovered (p.E167K) to be highly associated with increased hepatic fat content and reduced levels of plasma triglycerides and LDL cholesterol. In this review, we focus on the discovery of TM6SF2 and its role in VLDL secretion pathways. Human data suggest TM6SF2 is linked to hepatic steatosis and cardiovascular disease (CVD), hence understanding its metabolic pathways is of high scientific interest.Recent findings: Since its discovery, completed research studies in cell, rodent and human models have defined the role of TM6SF2 and its links to human disease. TM6SF2 resides in the endoplasmic reticulum (ER) and the ER-Golgi interface and helps with the lipidation of nascent VLDL, the main carrier of triglycerides from the liver to the periphery. Consistent results from cells and rodents indicated that the secretion of triglycerides is reduced in carriers of the p.E167K variant or when hepatic TM6SF2 is deleted. However, data for secretion of APOB, the main protein of VLDL particles responsible for triglycerides transport, are inconsistent.Summary: The identification of genetic variants that are highly associated with human disease presentation should be followed by the validation and investigation into the pathways that regulate disease mechanisms. In this review, we highlight the role of TM6SF2 and its role in processing of liver triglycerides.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"157-161"},"PeriodicalIF":4.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11168781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Familial hypercholesterolemia-Plus: is the metabolic syndrome changing the clinical picture of familial hypercholesterolemia? 家族性高胆固醇血症加：代谢综合征是否改变了家族性高胆固醇血症的临床表现？

IF 4.4 3区医学

Current opinion in lipidology Pub Date : 2024-04-22 DOI: 10.1097/mol.0000000000000938

Liam R Brunham

引用次数: 0