Current opinion in lipidology最新文献

The intracellular chylomicron highway: novel insights into chylomicron biosynthesis, trafficking, and secretion.

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-03-31 DOI: 10.1097/MOL.0000000000000983

Ankia Visser, M Mahmood Hussain, Jan Albert Kuivenhoven

{"title":"The intracellular chylomicron highway: novel insights into chylomicron biosynthesis, trafficking, and secretion.","authors":"Ankia Visser, M Mahmood Hussain, Jan Albert Kuivenhoven","doi":"10.1097/MOL.0000000000000983","DOIUrl":"10.1097/MOL.0000000000000983","url":null,"abstract":"Purpose of review: Chylomicron biosynthesis plays a vital role in supplying essential lipids and lipid soluble vitamins to peripheral tissues for various functions. Despite this, the intracellular synthesis, trafficking, and secretion of chylomicrons remains only partly understood. The purpose of this review is to summarize the role of established proteins in this process and bring attention to recently identified proteins to provide an up-to-date model of chylomicron biosynthesis.Recent findings: Recently, several proteins have been shown to play a role in the initial formation and lipidation of chylomicrons at the endoplasmic reticulum (ER), which include: TM6SF2, PLA2G12B, PRAP1, and SURF4. In addition, mitochondria have been implicated in chylomicron metabolism, but mechanistic insight is missing. The trafficking of chylomicrons from the ER to the Golgi, and the subsequent trafficking from the Golgi to the basolateral side of enterocytes, however, remains a mystery.Summary: Progress in the chylomicron biosynthesis field is largely associated with findings in VLDL biosynthesis. In addition, increased insight in events after prechylomicrons leave the ER is needed. Given the important role of chylomicron biosynthesis in whole-body lipid metabolism, further research into the molecular mechanisms is warranted.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728768","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

The need for national and international registries of patients with elevated lipoprotein(a).

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-03-20 DOI: 10.1097/MOL.0000000000000982

Adam I Kramer, Iulia Iatan, Liam R Brunham

引用次数: 0

Therapeutic advances in the Lp(a) battle: what do we know and what are the most awaited novelties in the field ?

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-03-20 DOI: 10.1097/MOL.0000000000000981

Marc Jean-Gilles, Baris Gencer

{"title":"Therapeutic advances in the Lp(a) battle: what do we know and what are the most awaited novelties in the field ?","authors":"Marc Jean-Gilles, Baris Gencer","doi":"10.1097/MOL.0000000000000981","DOIUrl":"https://doi.org/10.1097/MOL.0000000000000981","url":null,"abstract":"Purpose of review: To review the latest advances in lipoprotein(a) [Lp(a)] treatment, focusing on the impact of currently available lipid-lowering therapies and highlighting the highly anticipated and most developed RNA-based therapies.Recent findings: Lp(a) is a key genetically determined cardiovascular risk modifier linked to myocardial infarction and calcific aortic stenosis development and progression. Conventional lipid-lowering therapies have no substantial effect on circulating Lp(a) levels, leading current guidelines to focus on managing traditional cardiovascular risk factors. New therapies, including antisense oligonucleotides and small interfering RNAs, target Lipoprotein(A) [LPA] gene translation to reduce apo(a) synthesis and Lp(a) particles formation. The most advanced candidates, pelacarsen, olpasiran, and lepodisiran, have shown promising Lp(a) reductions, ranging from -35% to -101% in Phase 1 and 2 trials. Phase 3 studies will clarify their effects on cardiovascular outcomes and address concerns about extremely low Lp(a) levels and safety.Summary: The RNA-based agents pelacarsen, olpasiran, and lepodisiran represent the most advanced developments in this field. Ongoing Phase 3 trials, expected to be finalized between 2025 and 2029, will be crucial in determining their efficacy in improving cardiovascular outcomes and their safety profiles.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699751","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

Familial hypercholesterolemia in pregnancy.

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-03-07 DOI: 10.1097/MOL.0000000000000980

Fahad Alnouri, Frederick J Raal

{"title":"Familial hypercholesterolemia in pregnancy.","authors":"Fahad Alnouri, Frederick J Raal","doi":"10.1097/MOL.0000000000000980","DOIUrl":"https://doi.org/10.1097/MOL.0000000000000980","url":null,"abstract":"Purpose of review: Individuals with familial hypercholesterolemia (FH), particularly those with homozygous FH (HoFH) who have markedly elevated LDL-cholesterol (LDL-C) levels from birth, present with unique complications during pregnancy. This review explores the complexities of FH care during pregnancy.Recent findings: The worldwide burden of FH is much greater than previously thought. Still, underdiagnosis and undertreatment are substantial, necessitating increased awareness, genetic screening efforts, and better access to diagnostic tools. Although there is guidance for implementing best practices in the care of FH, including pregnancy, currently, there are no evidence-based guidelines that address HoFH at the time of pregnancy planning or during pregnancy and lactation.Summary: FH management in pregnancy requires a reasonable balance between fetal safety and maternal LDL-C control. Discontinuing lipid-lowering medication during pregnancy and the postpartum period needs to be considered, and in severe cases, lipoprotein apheresis may be an appropriate substitute. Comprehensive patient care requires coordination by genetic counselors, cardiologists, lipidologists, and obstetricians. The management of HoFH in pregnancy requires further research efforts, enhancement of public knowledge, and worldwide cooperation. By focusing on these areas, we can make significant progress in diagnostics and develop efficient management plans for improving outcomes among pregnant women with HoFH.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595762","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

Leveraging drug-target Mendelian randomization for tailored lipoprotein-lipid lowering.

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-02-21 DOI: 10.1097/MOL.0000000000000977

Eloi Gagnon, Benoit J Arsenault

{"title":"Leveraging drug-target Mendelian randomization for tailored lipoprotein-lipid lowering.","authors":"Eloi Gagnon, Benoit J Arsenault","doi":"10.1097/MOL.0000000000000977","DOIUrl":"https://doi.org/10.1097/MOL.0000000000000977","url":null,"abstract":"Purpose of review: The study of naturally occurring genetic variation in human populations has laid the foundation for proprotein converts subtilisin/kexin type 9 inhibitors, and more recently new classes of lipid-lowering drugs such as lipoprotein(a) inhibitors and lipoprotein lipase pathway activators. These emerging therapies lower plasma lipoprotein-lipid levels that are not adequately managed by traditional low-density lipoprotein (LDL) cholesterol-lowering medications. By targeting different risk factors, these therapies could help manage the important residual cardiovascular risk of LDL cholesterol medications.Recent findings: We review the latest insights into the pharmacological and genetic modulation of these new therapeutic targets. We highlight that the drugs remarkably recapitulate the lipid effects observed in genetic studies. In addition to lowering lipoprotein-lipid levels, robust genetic evidence support that these drugs may prevent cardiometabolic outcomes.Summary: Emerging lipid-lowering therapies could launch a new era for preventive medicine in which treatments are optimally tailored to patient's lipoprotein-lipid profiles.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457200","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

Emerging agents targeting triglycerides.

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-02-19 DOI: 10.1097/MOL.0000000000000979

Yash Prakash, Deepak L Bhatt, Waqas A Malick

{"title":"Emerging agents targeting triglycerides.","authors":"Yash Prakash, Deepak L Bhatt, Waqas A Malick","doi":"10.1097/MOL.0000000000000979","DOIUrl":"https://doi.org/10.1097/MOL.0000000000000979","url":null,"abstract":"Purpose of review: Hypertriglyceridemia (HTG), which arises from defects in triglyceride-rich lipoprotein (TRL) metabolism, is associated with increased morbidity and mortality from pancreatitis and atherosclerotic cardiovascular disease. Traditional therapies, including fibrates and omega-3 fatty acids, have shown limited efficacy in controlling triglyceride (TG) levels and cardiovascular risk. This review explores the role of emerging therapies that target TG and TRL metabolism via novel biochemical pathways.Recent findings: Apolipoprotein C-III inhibitors appear most effective for patients with variants of severe HTG, particularly multifactorial and familial chylomicronemia syndromes, by enhancing TRL metabolism through both lipoprotein lipase-dependent and independent mechanisms. Angiopoeitin-like proteins 3 and 4 inhibitors appear most useful for mixed hyperlipidemia, with favorable effects across the entire spectrum of apoB-containing atherogenic lipoproteins. For patients with HTG and concomitant complications of insulin resistance, including metabolic associated steatotic liver disease and type 2 diabetes mellitus, fibroblast growth factor-21 analogs may provide significant benefit.Summary: HTG is a diverse condition. Apolipoprotein C-III inhibitors, angiopoeitin-like proteins 3 and 4 inhibitors, and fibroblast growth factor-21 analogs represent significant advancements in the treatment of HTG, offering new hope for effectively managing this condition across its full spectrum of disease.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448476","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

The potential of circulating nonesterified fatty acids and sphingolipids in the biological understanding of cognitive decline and dementia. 循环非酯化脂肪酸和鞘脂在认知能力下降和痴呆的生物学理解中的潜力。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-02-01 Epub Date: 2024-12-06 DOI: 10.1097/MOL.0000000000000968

Kristine F Moseholm, Josefine T Meineche, Majken K Jensen

{"title":"The potential of circulating nonesterified fatty acids and sphingolipids in the biological understanding of cognitive decline and dementia.","authors":"Kristine F Moseholm, Josefine T Meineche, Majken K Jensen","doi":"10.1097/MOL.0000000000000968","DOIUrl":"10.1097/MOL.0000000000000968","url":null,"abstract":"Purpose of review: Cognitive decline and late-onset dementia pose significant challenges in aging societies, and many dementia cases could be prevented or delayed through modification of associated risk factors, many of which are tied to cardiovascular and metabolic dysfunction. As individuals age, the blood-brain barrier becomes more permeable, easing the exchange of molecules between the bloodstream and the brain. Consequently, blood-based biological markers (so-called biomarkers) provide a minimally invasive and accessible means of accessing molecular changes associated with aging and neurodegeneration.Recent findings: Circulating free fatty acids, also called nonesterified fatty acids (NEFAs), and sphingolipids are associated with cardiovascular disease, insulin resistance, and diabetes; thus, could be promising candidates as biomarkers for cognitive decline and dementia.Summary: The opportunity to study such minimally invasive biomarkers further opens up potential new avenues for improved understanding of the underlying biology of diseases of the brain.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"27-37"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784470","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

Atherogenic low-density lipoprotein and cardiovascular risk. 致动脉粥样硬化低密度脂蛋白与心血管风险。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-02-01 Epub Date: 2024-12-06 DOI: 10.1097/MOL.0000000000000963

Javier Hernando-Redondo, Olga Castañer Niño, Montse Fitó

{"title":"Atherogenic low-density lipoprotein and cardiovascular risk.","authors":"Javier Hernando-Redondo, Olga Castañer Niño, Montse Fitó","doi":"10.1097/MOL.0000000000000963","DOIUrl":"10.1097/MOL.0000000000000963","url":null,"abstract":"Purpose of review: Despite reductions in low-density lipoprotein (LDL) cholesterol (LDLc), residual cardiovascular risk remains due to factors beyond lipoprotein levels, such as LDL particle count, size, electronegativity and modifications. Technological advances allow detailed profiling of LDL particles, offering potential biomarkers for diagnosis, prognosis, and treatment of cardiovascular disease (CVD). The aim of this review is to provide an updated overview of the state of knowledge in the field of LDL atherosclerotic role, which is evolving rapidly due to technological advances in biomarker measurement and applications.Recent findings: While small dense LDL has been linked to increased CVD risk, current approaches favor a comprehensive evaluation of all lipoprotein subtypes, as this is a more feasible and standardized method. The atherogenic potential of circulating oxidized LDL (oxLDL) may be the key factor in the onset and progression of atherosclerosis. Thus, elevated oxLDL levels are recognized as a marker of increased CVD risk in both general and high-risk populations, although further research is needed to clarify some conflicting findings. The oxidized LDL receptor 1 (LOX-1) has emerged as a promising target for immunotherapy and innovative drug delivery strategies to modulate atherosclerosis.Summary: A panel of biomarkers related to LDL atherogenicity may help predict future ischemic events. An atheroprotective diet and increased physical activity could improve LDL oxidation. OxLDL has become a target for immunomodulatory antiatherosclerosis therapy and delivering LDL-based nanocarriers holds promise for both imaging and therapeutics.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"8-13"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784469","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

Preeclampsia and fetal growth restriction: does novel proteomics reveal immunological possible candidate biomarkers? 子痫前期和胎儿生长受限：新的蛋白质组学是否揭示了可能的免疫候选生物标志物？

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-02-01 Epub Date: 2024-11-28 DOI: 10.1097/MOL.0000000000000965

Marie Winther, Morten Hanefeld Dziegiel, Steffen Ullitz Thorsen

{"title":"Preeclampsia and fetal growth restriction: does novel proteomics reveal immunological possible candidate biomarkers?","authors":"Marie Winther, Morten Hanefeld Dziegiel, Steffen Ullitz Thorsen","doi":"10.1097/MOL.0000000000000965","DOIUrl":"10.1097/MOL.0000000000000965","url":null,"abstract":"Purpose of review: The aim of this review is to explore a possible link between immunological candidate proteins, identified through modern proteomic techniques, and preeclampsia (PE) and fetal growth restriction (FGR).Recent findings: Proteomics has become a promising tool in the search for disease pathways, drug targets, and biomarkers. PE and FGR are adverse pregnancy complications with supposed immunological involvement in their pathogenesis, but no circulating immunological biomarkers are currently established for diagnosis and risk stratification. Several proteomic studies have aimed to identify PE and FGR biomarkers - often with varying results across studies. However, proteomics has revealed altered expression of human leukocyte antigen-I in PE cases, which is supported in Genome-wide association study (GWAS) studies. Proteomic results support the heterogeneous nature of PE by identification of molecular subgroups - including subgroups characterized by immune-related proteins e.g. CXCL10. No specific immunological markers are found on FGR, but differences in overall plasma proteomic signature have been suggested.Summary: Proteomics certainly holds great potential. The immunological component in PE and FGR are still unclarified, but improvements in proteomic technologies may provide both definition of disease subgroups and subsequent discovery of biomarkers and targeted analysis within each subgroup.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"21-26"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750221","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

Editorial introductions. 编辑介绍。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2025-02-01 Epub Date: 2025-01-03 DOI: 10.1097/MOL.0000000000000969

引用次数: 0