Current opinion in lipidology最新文献

SPRINGing off the lock: the role of SPRING in S1P activity and SREBP-regulated lipid metabolism. SPRING off the lock: SPRING在S1P活性和srebp调节的脂质代谢中的作用。

IF 4.6 3区医学

Current opinion in lipidology Pub Date : 2025-10-01 Epub Date: 2025-08-01 DOI: 10.1097/MOL.0000000000001003

Ilaria Micallo, Ashley V Bullington, Daniel L Kober, Noam Zelcer

{"title":"SPRINGing off the lock: the role of SPRING in S1P activity and SREBP-regulated lipid metabolism.","authors":"Ilaria Micallo, Ashley V Bullington, Daniel L Kober, Noam Zelcer","doi":"10.1097/MOL.0000000000001003","DOIUrl":"10.1097/MOL.0000000000001003","url":null,"abstract":"Purpose of review: Lipid metabolism and de-novo lipogenesis (DNL) is broadly controlled by the SREBP transcription factors. These transcription factors are matured from membrane-anchored precursor proteins by the proteolytic actions of the proteases S1P and S2P. In this review, we summarize the current understanding of SPRING, a recently identified activator of S1P.Recent findings: Recent studies of SPRING using animal, cellular, biochemical, and biophysical methods have established SPRING as a core component of the SREBP machinery. Deletion of SPRING in cells and animal livers specifically reduces SREBP activity yet leaves other S1P substrates intact, demonstrating an SREBP-specific role for SPRING in licensing S1P activity. Mechanistic biochemical and structural studies revealed that SPRING activates S1P by competitively displacing its inhibitory pro-domain and elucidated how small molecule inhibition of S1P can be accomplished.Summary: Current studies have shown how SPRING activates S1P and uncovered a critical role for SPRING in the SREBP pathway. Further studies are warranted to understand this emerging, connection between SPRING and the regulation of DNL through SREBP.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"276-283"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759392","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

Therapeutic lowering of lipoprotein(a): implications for improving outcomes in patients with peripheral arterial disease. 治疗性降低脂蛋白(a)：改善外周动脉疾病患者预后的意义

IF 4.6 3区医学

Current opinion in lipidology Pub Date : 2025-10-01 Epub Date: 2025-07-21 DOI: 10.1097/MOL.0000000000001002

Stephen J Nicholls

{"title":"Therapeutic lowering of lipoprotein(a): implications for improving outcomes in patients with peripheral arterial disease.","authors":"Stephen J Nicholls","doi":"10.1097/MOL.0000000000001002","DOIUrl":"10.1097/MOL.0000000000001002","url":null,"abstract":"Purpose of review: To identify the opportunity of targeting patients with elevated lipoprotein(a) [Lp(a)] in patients with peripheral arterial disease (PAD).Recent findings: Lp(a) plays a causal role in atherosclerotic cardiovascular disease. Cohort studies demonstrate that elevated Lp(a) levels independently associate with an increased risk of developing PAD. Patients with manifest PAD have a high residual cardiovascular risk, despite use of traditional lipid lowering. The current approach to treatment of patients with high Lp(a) levels involves intensification of management of conventional cardiovascular risk factors and consideration of use of aspirin. In recent years, therapeutic programs have developed injectable RNA targeted agents and a small molecule Lp(a) assembly disrupter that are well tolerated and produce effective Lp(a) lowering. Many of these agents are being evaluated in large cardiovascular outcomes trials. Advances have also looked to develop gene/base editing and epigenetic treatments to lower Lp(a).Summary: These studies demonstrate that Lp(a) plays an important role in cardiovascular disease, including PAD. However, it remains to be determined if more effective Lp(a) lowering will translate to cardiovascular benefit. If this does prove to be the case, integration of Lp(a) testing and therapeutics has the potential to transform clinical outcomes in people living with PAD.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"232-237"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689472","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

Cycling of metabolic states and metabolites as drivers of atherosclerosis. 代谢状态和代谢物作为动脉粥样硬化驱动因素的循环。

IF 4.6 3区医学

Current opinion in lipidology Pub Date : 2025-10-01 Epub Date: 2025-07-30 DOI: 10.1097/MOL.0000000000001004

Franziska Krautter, Edward A Fisher

{"title":"Cycling of metabolic states and metabolites as drivers of atherosclerosis.","authors":"Franziska Krautter, Edward A Fisher","doi":"10.1097/MOL.0000000000001004","DOIUrl":"10.1097/MOL.0000000000001004","url":null,"abstract":"Purpose of review: Cardiovascular diseases (CVDs) are a leading cause of death worldwide. While it is well known that obesity, dyslipidemia and diabetes are major risk factors of CVD, observational clinical studies have shown that variability in body weight, circulating LDL-cholesterol (LDL-C) or glucose levels further increase this risk. The underlying mechanisms, however, leading to increased risk of CVD due to metabolic cycling are not well understood.Recent findings: Recent studies have shown that metabolic cycling can cause reprogramming of immune cells and their progenitors. Weight, LDL-C, or glucose cycling induced myelopoiesis, monocytosis and/or altered immune cell functions. This resulted in a heightened immune response, ultimately worsening atherosclerosis.Summary: Even though there are differences in how metabolic cycling is measured in clinical and basic research studies, the conclusion remains the same: metabolic cycling increases CVD severity. Some studies have highlighted the role of reprogramming of myeloid cells and their progenitors in progression of atherosclerosis due to metabolic cycling, but further research is required to better understand the mechanisms behind it.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"251-257"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752649","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

Beyond cholesterol: linking the conformation of apolipoprotein B to atherogenesis. 胆固醇之外：将载脂蛋白B的构象与动脉粥样硬化联系起来。

IF 4.6 3区医学

Current opinion in lipidology Pub Date : 2025-10-01 Epub Date: 2025-06-23 DOI: 10.1097/MOL.0000000000000997

Katariina Öörni, Martina B Lorey

{"title":"Beyond cholesterol: linking the conformation of apolipoprotein B to atherogenesis.","authors":"Katariina Öörni, Martina B Lorey","doi":"10.1097/MOL.0000000000000997","DOIUrl":"10.1097/MOL.0000000000000997","url":null,"abstract":"Purpose of review: This review integrates recent structural and biochemical insights into apolipoprotein B (apoB) containing lipoproteins to highlight how factors beyond cholesterol levels contribute to atherosclerosis.Recent findings: Emerging evidence demonstrates that the atherogenic potential of apoB-containing lipoproteins varies substantially both between and within lipoprotein classes. Recent studies using high-resolution cryo-electron microscopy, crosslinking mass spectrometry, and computational modeling reveal that even subtle differences in lipoprotein composition, particle size, and lipid spatial organization can significantly alter the conformation and dynamic behavior of apoB on the particle surface. These conformational shifts influence a variety of lipoprotein characteristics such as the stability of the particle, their ability to interact with receptors and enzymes, and their proatherogenic potential as measured by the propensity of lipoproteins to bind to proteoglycans of the arterial wall or to undergo modification and aggregation.Summary: In this review, we discuss how novel structural and functional information can refine our understanding of the distinct properties of apoB-containing lipoproteins and their role in atherosclerosis and lipid accumulation. Understanding of the specific features related to the proatherogenic behavior of the lipoproteins helps in understanding the complexities of atherogenesis and cardiovascular risk beyond cholesterol.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"226-231"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474216","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

Editorial introduction. 编辑介绍。

IF 4.6 3区医学

Current opinion in lipidology Pub Date : 2025-10-01 Epub Date: 2025-09-04 DOI: 10.1097/MOL.0000000000001006

引用次数: 0

Peripheral arterial disease associated with elevated lipoprotein(a): a review of the evidence and treatment approaches. 外周动脉疾病与脂蛋白升高相关(a)：证据和治疗方法综述

IF 4.6 3区医学

Current opinion in lipidology Pub Date : 2025-10-01 Epub Date: 2025-06-13 DOI: 10.1097/MOL.0000000000000999

Harpreet S Bhatia, Sonar Dalal, Elsie Ross

{"title":"Peripheral arterial disease associated with elevated lipoprotein(a): a review of the evidence and treatment approaches.","authors":"Harpreet S Bhatia, Sonar Dalal, Elsie Ross","doi":"10.1097/MOL.0000000000000999","DOIUrl":"10.1097/MOL.0000000000000999","url":null,"abstract":"Purpose of review: Peripheral arterial disease (PAD) is an atherosclerotic and thrombotic disease associated with substantial morbidity and mortality. Although risk factors for PAD are mostly modifiable, prognosis remains poor, and patients are at a high risk of cardiovascular events. This review aims to summarize current evidence surrounding the role of lipoprotein(a) (Lp[a]) in PAD and examines the available data on lipoprotein apheresis as an effective management approach for patients with PAD with elevated Lp(a).Recent findings: Evidence strongly indicates that elevated Lp(a) is a causal and independent risk factor for PAD and is associated with PAD severity and increased risk of adverse outcomes, including major adverse cardiovascular events and major adverse limb events. Proprotein convertase subtilisin/kexin type 9 inhibitors can modestly reduce Lp(a) levels, and several Lp(a)-lowering therapies are currently under investigation. Prospective cohort studies in patients with PAD with elevated Lp(a) have reported clinical benefits of lipoprotein apheresis, including reduction of cardiovascular event risk.Summary: Limited treatment options exist for patients with PAD and elevated Lp(a). Lipoprotein apheresis is currently the only treatment option approved specifically for lowering Lp(a) levels.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"238-250"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282772","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

The complex pro-atherosclerotic role of lipoprotein(a): a multiplicity of cellular targets. 脂蛋白的复杂促动脉粥样硬化作用(a)：细胞靶点的多样性。

IF 4.6 3区医学

Current opinion in lipidology Pub Date : 2025-10-01 Epub Date: 2025-08-01 DOI: 10.1097/MOL.0000000000001000

Julia M Assini, Michael B Boffa, Marlys L Koschinsky

{"title":"The complex pro-atherosclerotic role of lipoprotein(a): a multiplicity of cellular targets.","authors":"Julia M Assini, Michael B Boffa, Marlys L Koschinsky","doi":"10.1097/MOL.0000000000001000","DOIUrl":"10.1097/MOL.0000000000001000","url":null,"abstract":"Purpose of review: Elevated plasma lipoprotein(a) (Lp(a)) is a causal and independent risk factor for atherosclerotic cardiovascular disease; therefore, understanding the fundamental mechanisms underlying Lp(a)-mediated pathogenesis is of significant clinical importance. This review summarizes recent advances in understanding the precise cellular targets of Lp(a) in atherogenesis, uncovering potential therapeutic avenues worth exploring.Recent findings: Genetic evidence reveals that Lp(a) is six-fold more atherogenic per particle than LDL, and clinical imaging studies show increased atherosclerotic plaque burden and severity in patients with elevated Lp(a). A novel study using human monocytes uncovered diacylglycerols and lysophosphatidic acid as lipid species that contribute to the pro-inflammatory impacts of Lp(a), independent of the known pro-inflammatory oxidized phospholipids. The identification of a novel cell-surface receptor on endothelial cells involved in Lp(a) uptake offers another exploratory direction in vascular cells involved in atherosclerosis. Several studies have also pointed to accelerated coagulation as a potential target of Lp(a), involving Lp(a)-mediated impacts on platelet aggregation and monocyte tissue factor expression.Summary: An understanding of these cell-specific targets of Lp(a) in atherogenesis will aid the Lp(a) field in identifying novel therapeutic targets for patients with elevated Lp(a), for whom few available therapeutic strategies currently exist.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"268-275"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759393","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

Lipoprotein(a) and peripheral artery disease: contemporary evidence and therapeutic advances. 脂蛋白(a)和外周动脉疾病：当代证据和治疗进展

IF 4.6 3区医学

Current opinion in lipidology Pub Date : 2025-10-01 Epub Date: 2025-05-21 DOI: 10.1097/MOL.0000000000000998

Shivshankar Thanigaimani, Maarisha Kumar, Jonathan Golledge

{"title":"Lipoprotein(a) and peripheral artery disease: contemporary evidence and therapeutic advances.","authors":"Shivshankar Thanigaimani, Maarisha Kumar, Jonathan Golledge","doi":"10.1097/MOL.0000000000000998","DOIUrl":"10.1097/MOL.0000000000000998","url":null,"abstract":"Purpose of review: Peripheral artery disease (PAD) is a major cause of global health burden, including amputation and impaired quality of life. This review examines the evidence implicating lipoprotein(a) [Lp(a)] in PAD, which is timely as novel therapies lowering Lp(a) are currently being tested in several clinical trials.Recent findings: Human observational studies demonstrate strong associations between elevated Lp(a) levels and increased risk of PAD incidence, severity of chronic limb-threatening ischemia, and major adverse limb events. Emerging therapies including small interfering RNA, antisense oligonucleotides, proprotein convertase subtilisin-kexin type 9 inhibitors and lipoprotein apheresis demonstrate significant Lp(a)-lowering effects. However, whether these treatments benefit patients with PAD is currently unknown.Summary: Lp(a) may be involved in PAD pathogenesis. Lp(a)-lowering therapies may significantly reduce PAD-related events and improve outcomes. Future studies are needed to test Lp(a)-lowering therapies in people with PAD and to explore how the association of Lp(a) varies in different sexes and ethnicities and understand mechanisms by which Lp(a) may contribute to limb ischemia.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"258-267"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109509","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 intestine and cardiovascular disease. 肠道和心血管疾病。

IF 4.6 3区医学

Current opinion in lipidology Pub Date : 2025-10-01 Epub Date: 2025-07-21 DOI: 10.1097/MOL.0000000000001001

Samuel C Delk, Srinivasa T Reddy, Alan M Fogelman

{"title":"The intestine and cardiovascular disease.","authors":"Samuel C Delk, Srinivasa T Reddy, Alan M Fogelman","doi":"10.1097/MOL.0000000000001001","DOIUrl":"10.1097/MOL.0000000000001001","url":null,"abstract":"Purpose of review: A review of recent publications demonstrating the important role of the intestine in the pathogenesis of cardiovascular disease.Recent findings: At baseline (≥ 6 months since myocardial infarction), the pattern of fecal microbiota and blood LPS levels after a meal predicted risk for new major adverse cardiovascular events over the next 7 years. In intestine, tryptophan is metabolized primarily by the kynurenine pathway, which is regulated by the enzyme indoleamine-2,3-dioxygenase 1 (IDO1). Tryptophan flow into the kynurenine pathway limits its availability for the formation of microbiota-derived indole derivatives including butyrate, and limits availability of tryptophan for the 5-hydroxytryptamine (5-HT or serotonin) pathway. Feeding Ldlr-/- mice a high-fat high-cholesterol diet (HFD+HCD) increased intestinal IDO1 activity, decreased levels of tryptophan, fecal butyrate, and 5-HT. Ldlr-/- mice deficient in intestinal Ido1 ( Ldlr-/-Ido1-/- ) on HFD+HCD had increased intestinal levels of 5-HT, increased gut permeability, increased gut inflammation, increased LPS, and increased aortic atherosclerosis. Ldlr-/- mice fed HFD+HCD and treated with a 5-HT pathway inhibitor had increased fecal indole levels, improved gut-barrier, increased antimicrobial peptide levels, and decreased aortic atherosclerosis without a change in plasma cholesterol.Summary: These studies demonstrate the importance of microbiota-derived products and intestinal tryptophan metabolism in atherosclerosis.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"221-225"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689471","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

Macrophage cannibalism: efferocytosis in atherosclerosis. 巨噬细胞自相残杀：动脉粥样硬化中的efferocytosis。

IF 4.6 3区医学

Current opinion in lipidology Pub Date : 2025-08-25 DOI: 10.1097/MOL.0000000000001010

Amy A Baxter, Ivan K H Poon, Denuja Karunakaran

{"title":"Macrophage cannibalism: efferocytosis in atherosclerosis.","authors":"Amy A Baxter, Ivan K H Poon, Denuja Karunakaran","doi":"10.1097/MOL.0000000000001010","DOIUrl":"10.1097/MOL.0000000000001010","url":null,"abstract":"Purpose of review: This review explores the evolving understanding of efferocytosis - the clearance of dead or dying cells by phagocytes - in the context of atherosclerosis. It highlights recent discovers in cell death modalities, impaired clearance mechanisms and emerging therapeutic strategies aimed at restoring efferocytosis to stabilize plaques and resolve inflammation.Recent findings: Recent studies have expanded the scope of efferocytosis beyond apoptotic cells to include other pro-inflammatory cell death modes, including pyroptosis, necroptosis and ferroptosis, revealing context-dependent clearance efficiency and immunological outcomes. Novel mechanisms of impaired efferocytosis have been identified, including CD47- or CD147-mediated inhibition, efferocyte metabolic reprogramming and age-related MerTK cleavage. Therapeutic advances include nanoparticle-mediated delivery of SHP-1 inhibitors, engineered efferocytotic receptors, and treatment with resolvin D1 to enhance efferocytosis and reduce inflammation.Summary: Efferocytosis is a critical process in maintaining vascular homeostasis and preventing plaque rupture in atherosclerosis. Its impairment contributes to necrotic core expansion and chronic inflammation. Advances in understanding the molecular regulation of efferocytosis and its therapeutic modulation offer new avenues for intervention. Targeting efferocytosis may complement lipid-lowering and/or anti-inflammatory therapies, representing a promising strategy for cardiovascular disease management.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014083","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