W Sean Davidson, Tomas Vaisar, Jay W Heinecke, Karin E Bornfeldt
{"title":"Distinct roles of size-defined HDL subpopulations in cardiovascular disease.","authors":"W Sean Davidson, Tomas Vaisar, Jay W Heinecke, Karin E Bornfeldt","doi":"10.1097/MOL.0000000000000959","DOIUrl":"10.1097/MOL.0000000000000959","url":null,"abstract":"<p><strong>Purpose of review: </strong>Doubts about whether high-density lipoprotein-cholesterol (HDL-C) levels are causally related to atherosclerotic cardiovascular disease (CVD) risk have stimulated research on identifying HDL-related metrics that might better reflect its cardioprotective functions. HDL is made up of different types of particles that vary in size, protein and lipid composition, and function. This review focuses on recent findings on the specific roles of HDL subpopulations defined by size in CVD.</p><p><strong>Recent findings: </strong>Small HDL particles are more effective than larger particles at promoting cellular cholesterol efflux because apolipoprotein A-I on their surface better engages ABCA1 (ATP binding cassette subfamily A member 1). In contrast, large HDL particles bind more effectively to scavenger receptor class B type 1 on endothelial cells, which helps prevent LDL from moving into the artery wall. The specific role of medium-sized HDL particles, the most abundant subpopulation, is still unclear.</p><p><strong>Summary: </strong>HDL is made up of subpopulations of different sizes of particles, with selective functional roles for small and large HDLs. The function of HDL may depend more on the size and composition of its subpopulations than on HDL-C levels. Further research is required to understand how these different HDL subpopulations influence the development of CVD.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"111-118"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12003705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496782","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}
Isaiah Little, Stephanie Bersie, Elizabeth F Redente, Alexandra L McCubbrey, Elizabeth J Tarling
{"title":"Alveolar macrophages: guardians of the alveolar lipid galaxy.","authors":"Isaiah Little, Stephanie Bersie, Elizabeth F Redente, Alexandra L McCubbrey, Elizabeth J Tarling","doi":"10.1097/MOL.0000000000000987","DOIUrl":"10.1097/MOL.0000000000000987","url":null,"abstract":"<p><strong>Purpose of review: </strong>As the primary guardians at the air-surface interface, the functional profile of alveolar macrophages (AM) is wide-ranging from establishment of the alveolar niche, homeostatic maintenance of surfactant levels, to pathogen clearance and resolution and repair processes. Alveolar lipid homeostasis is disturbed in chronic lung diseases and contributes to disease pathogenesis through extracellular localization in the alveolar lumen or intracellular accumulation in AM. This review aims to provide a focused overview of the state of knowledge of AM, their ontogeny and development during health and disease, and how dysregulated AM lipids play a key role in disease processes, from initiation to resolution.</p><p><strong>Recent findings: </strong>While lipid-laden macrophages are observed across a broad spectrum of lung diseases, their occurrence has largely been considered consequential. Recent advances in lipidomic profiling of single cell types has revealed that disturbances to lipid homeostasis occur early in disease in tissue-resident cells. Comparisons between inflammatory and fibrotic injury models reveal specific alveolar macrophage subsets with different lipid utilization that contribute to the disease process.</p><p><strong>Summary: </strong>Understanding the intricate web of AM population seeding and development and how this niche is perturbed by lipid disturbances may help provide leverage for new interventions.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"153-162"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779397","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}
{"title":"Emerging agents targeting triglycerides.","authors":"Yash Prakash, Deepak L Bhatt, Waqas A Malick","doi":"10.1097/MOL.0000000000000979","DOIUrl":"10.1097/MOL.0000000000000979","url":null,"abstract":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>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.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"119-129"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","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}
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":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>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.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"145-152"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052055/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The need for national and international registries of patients with elevated lipoprotein(a).","authors":"Adam I Kramer, Iulia Iatan, Liam R Brunham","doi":"10.1097/MOL.0000000000000982","DOIUrl":"10.1097/MOL.0000000000000982","url":null,"abstract":"<p><strong>Purpose of review: </strong>Elevated lipoprotein(a) [Lp(a)] is a genetically determined independent risk factor for atherosclerotic cardiovascular disease (ASCVD). Current guidelines recommend universal testing of Lp(a) once in an individual's lifetime, with risk factor management intensification for those with elevated levels. However, there is a paucity of real-world data about how patients with elevated Lp(a) are managed and about their associated cardiovascular risk. The purpose of this review is to discuss recent progress in the establishment of registries of patients with elevated Lp(a).</p><p><strong>Recent findings: </strong>Multiple registries that include patients with elevated Lp(a) have been established in various countries. These studies will provide a snapshot of the global burden of this condition and the current patterns of treatment of this patient population.</p><p><strong>Summary: </strong>Elevated Lp(a) is a common but underdiagnosed risk factor for ASCVD. National and international registries are needed to expand our understanding and improve the treatment of this condition.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"105-110"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699805","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}
{"title":"Familial hypercholesterolemia in pregnancy.","authors":"Fahad Alnouri, Frederick J Raal","doi":"10.1097/MOL.0000000000000980","DOIUrl":"10.1097/MOL.0000000000000980","url":null,"abstract":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>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.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"138-144"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","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}
{"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":"10.1097/MOL.0000000000000981","url":null,"abstract":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>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.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"130-137"},"PeriodicalIF":3.8,"publicationDate":"2025-06-01","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}
{"title":"What is the phenotype of heterozygous lipoprotein lipase deficiency?","authors":"Robert A Hegele","doi":"10.1097/MOL.0000000000000974","DOIUrl":"https://doi.org/10.1097/MOL.0000000000000974","url":null,"abstract":"<p><strong>Purpose of review: </strong>Genetic testing of patients with severe hypertriglyceridemia often identifies a single heterozygous pathogenic variant in the LPL gene. The complex and variable phenotype associated with this genotype is the topic of this review.</p><p><strong>Recent findings: </strong>Previous research showed that heterozygosity for lipoprotein lipase deficiency is associated with reduced but variable post heparin lipolytic activity alongside inconsistent plasma lipid phenotypes ranging from normal to mild-to-moderate to severe hypertriglyceridemia. Recent research confirms and extends these observations, showing that a heterozygous individual can express a highly variable phenotype over time, depending on the presence of secondary factors. About 10% (range 8-20%) of patients with severe hypertriglyceridemia or multifactorial chylomicronemia syndrome are heterozygous for a rare pathogenic LPL variant, and a clinically relevant minority of these has recalcitrant or sustained hypertriglyceridemia.</p><p><strong>Summary: </strong>Heterozygosity for lipoprotein lipase deficiency predisposes to hypertriglyceridemia, which is sometimes severe depending on secondary factors, but is typically quite responsive to routine interventions such as diet, lifestyle and existing lipid-lowering therapies. However, many heterozygotes for pathogenic variants in LPL have completely normal plasma lipids.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":"36 2","pages":"96-103"},"PeriodicalIF":3.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971005","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}
Jacqueline S Dron, Pradeep Natarajan, Gina M Peloso
{"title":"The breadth and impact of the Global Lipids Genetics Consortium.","authors":"Jacqueline S Dron, Pradeep Natarajan, Gina M Peloso","doi":"10.1097/MOL.0000000000000966","DOIUrl":"10.1097/MOL.0000000000000966","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review highlights contributions of the Global Lipids Genetics Consortium (GLGC) in advancing the understanding of the genetic etiology of blood lipid traits, including total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, and non-HDL cholesterol. We emphasize the consortium's collaborative efforts, discoveries related to lipid and lipoprotein biology, methodological advancements, and utilization in areas extending beyond lipid research.</p><p><strong>Recent findings: </strong>The GLGC has identified over 923 genomic loci associated with lipid traits through genome-wide association studies (GWASs), involving more than 1.65 million individuals from globally diverse populations. Many loci have been functionally validated by individuals inside and outside the GLGC community. Recent GLGC studies show increased population diversity enhances variant discovery, fine-mapping of causal loci, and polygenic score prediction for blood lipid levels. Moreover, publicly available GWAS summary statistics have facilitated the exploration of lipid-related genetic influences on cardiovascular and noncardiovascular diseases, with implications for therapeutic development and drug repurposing.</p><p><strong>Summary: </strong>The GLGC has significantly advanced the understanding of the genetic basis of lipid levels and serves as the leading resource of GWAS summary statistics for these traits. Continued collaboration will be critical to further understand lipid and lipoprotein biology through large-scale genetic assessments in diverse populations.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"61-70"},"PeriodicalIF":4.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11888832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738724","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}