Current opinion in lipidology最新文献

From smooth to 'breaking bad': vascular smooth muscle cell phenotypic switching at the heart of plaque vulnerability. 从光滑到“绝命毒师”：斑块易损性核心的血管平滑肌细胞表型转换。

IF 4.5 3区医学

Current opinion in lipidology Pub Date : 2026-10-01 Epub Date: 2026-09-03 DOI: 10.1097/MOL.0000000000001056

Shevin C Fernando, Renjing Liu, Denuja Karunakaran

{"title":"From smooth to 'breaking bad': vascular smooth muscle cell phenotypic switching at the heart of plaque vulnerability.","authors":"Shevin C Fernando, Renjing Liu, Denuja Karunakaran","doi":"10.1097/MOL.0000000000001056","DOIUrl":"10.1097/MOL.0000000000001056","url":null,"abstract":"Purpose of review: Atherosclerosis persists despite LDL-lowering therapies, highlighting lipid-independent drivers of disease. This review examines vascular smooth muscle cell (VSMC) plasticity as a central determinant of plaque progression and stability and evaluates emerging therapeutic strategies targeting VSMC phenotypic transitions.Recent findings: VSMCs exhibit marked phenotypic plasticity, contributing to up to 50% of plaque foam cells and generating diverse states including macrophage-like, fibromyocyte, osteogenic, and intermediate populations. Key regulators such as Krüppel-like factor 4 (KLF4) and octamer-binding transcription factor 4 (OCT4) govern transitions between stabilising α-smooth muscle actin-positive (ACTA2 + ) cap-forming and destabilising lectin galactoside-binding soluble 3-positive (LGALS3 + ) inflammatory phenotypes. VSMC-derived foam cells display impaired cholesterol efflux and efferocytosis. Epigenetic reprogramming and oncogenic-like signalling, including nuclear factor kappa B (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), and mitogen-activated protein kinase (MAPK), underpin these changes. Emerging therapies include microRNA-based targeting of KLF4, chimeric antigen receptor regulatory T cells directed against oxidised LDL, nanoparticle systems targeting osteopontin, and fibroblast activation protein (FAP)-directed strategies.Summary: VSMC plasticity integrates inflammatory and epigenetic signals to drive plaque evolution. Targeting specific VSMC states offers a precision medicine approach to stabilise plaques while preserving vascular integrity.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"201-210"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148825149","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

Atherosclerosis resolution: strategies to remodel and resolve plaques. 动脉粥样硬化解决：重塑和解决斑块的策略。

IF 4.5 3区医学

Current opinion in lipidology Pub Date : 2026-10-01 Epub Date: 2026-08-12 DOI: 10.1097/MOL.0000000000001050

Emily Halbedl, Edward A Fisher

{"title":"Atherosclerosis resolution: strategies to remodel and resolve plaques.","authors":"Emily Halbedl, Edward A Fisher","doi":"10.1097/MOL.0000000000001050","DOIUrl":"10.1097/MOL.0000000000001050","url":null,"abstract":"Purpose of review: Despite aggressive cholesterol lowering, many patients continue to experience cardiovascular events (\"residual risk\"), emphasizing the need for novel risk reduction strategies. This review highlights recent advances in studying atherosclerosis resolution, with a focus on the key role played by plaque inflammation.Recent findings: Preclinical studies demonstrate that while atherosclerosis resolution can involve plaque size reductions, more important are changes in plaque remodeling, as measured by necrotic core, CD68 area, and collagen content. Resolution can be partially achieved with cholesterol lowering, inflammation resolution alone, or better yet, combination approaches. This review evaluates lipid-lowering strategies, as well as inflammation-targeting pathways involving efferocytosis, pro-resolving macrophages, platelets, and caloric restriction. Translational studies and clinical trials targeting inflammatory pathways, including interleukin (IL)-1β, IL-6, NLRP3, and pro-resolving mediators further support inflammation modulation as a therapeutic strategy.Summary: Many preclinical models of atherosclerosis resolution promote significant plaque remodeling by lipid-lowering, inflammation resolution, or combination approaches. Many recent and currently recruiting clinical trials are testing the benefits of inflammation resolution to further reduce cardiovascular risk in at-risk patients.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"170-176"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720587","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

Sitosterolemia: evolving strategies for earlier diagnosis. 谷固醇血症：早期诊断的发展策略。

IF 4.5 3区医学

Current opinion in lipidology Pub Date : 2026-10-01 Epub Date: 2026-09-03 DOI: 10.1097/MOL.0000000000001054

Annelise Genoux, Thibaut Jamme, Laurent O Martinez

{"title":"Sitosterolemia: evolving strategies for earlier diagnosis.","authors":"Annelise Genoux, Thibaut Jamme, Laurent O Martinez","doi":"10.1097/MOL.0000000000001054","DOIUrl":"10.1097/MOL.0000000000001054","url":null,"abstract":"Purpose of review: Sitosterolemia is a rare autosomal recessive lipid disorder caused by biallelic pathogenic variants in ABCG5 or ABCG8 , resulting in excessive intestinal absorption and impaired biliary excretion of plant sterols. Although historically considered exceptionally rare, recent genetic studies suggest the disorder is substantially underdiagnosed, with marked phenotypic heterogeneity ranging from xanthomas and premature atherosclerosis to hematologic abnormalities, and frequently mimics familial hypercholesterolemia. This review summarizes recent advances in the clinical, biological, and genetic diagnosis of sitosterolemia, with a focus on strategies that may facilitate earlier detection.Recent findings: Phytosterol quantification, particularly sitosterol, campesterol, and stigmasterol, remains indispensable for accurate diagnosis. Hematologic abnormalities, including hemolytic anemia, stomatocytosis, and macrothrombocytopenia, are increasingly recognized as valuable diagnostic clues complementing the biochemical approach. Expanded variant catalogs for ABCG5/ABCG8 and genome-wide association studies have revealed potentially polygenic contributions to phytosterol metabolism extending beyond these two genes. However, no specific guidelines have yet been established for cascade screening.Summary: Earlier diagnosis requires integration of clinical, biochemical, hematologic, and genetic data. Plasma phytosterol measurement remains the diagnostic cornerstone. Improved disease awareness, broader access to sterol testing, and expanded genetic screening may reduce diagnostic delays and enable timely management, including ezetimibe and dietary phytosterol restriction.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"196-200"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812379","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

HDL-associated proteins affecting CVD and systemic inflammation. 影响心血管疾病和全身炎症的高密度脂蛋白相关蛋白。

IF 4.5 3区医学

Current opinion in lipidology Pub Date : 2026-10-01 Epub Date: 2026-08-12 DOI: 10.1097/MOL.0000000000001052

Samuel C Delk, Srinivasa T Reddy

{"title":"HDL-associated proteins affecting CVD and systemic inflammation.","authors":"Samuel C Delk, Srinivasa T Reddy","doi":"10.1097/MOL.0000000000001052","DOIUrl":"10.1097/MOL.0000000000001052","url":null,"abstract":"Purpose of review: It has become clear that elevated HDL-C is not a reliable marker of protection against inflammation and cardiovascular disease (CVD). This review summarizes recent advances in understanding how HDL function is affected by its associated proteins, demonstrating that this is a more appropriate lens through which to assess HDL's protective capacity.Recent findings: Recent publications have demonstrated an inverse relationship between ApoM and clinical outcomes in chronic kidney disease and its concomitant cardiovascular indications. Mechanistic studies show that ApoM's regulation of mitochondrial function and autophagy are likely contributors to this effect. Additionally, ApoA-I, serum amyloid albumin (SAA), and SR-B1 have recently been highlighted as key regulators of atherogenesis through their ability to prevent LDL transcytosis and arterial entrapment by proteoglycans. Lastly, a novel mechanism is described wherein HDL-bound endotoxin is degraded through the endosome-lysosome pathway in an SR-B1-dependent manner, attenuating IL-1β activation. In the same study, inhibition of CETP (cholesterol ester transfer protein) increased HDL and improved mortality in a mouse model of sepsis, highlighting this pathway's importance and therapeutic potential of CETP inhibition, which is currently in key clinical trials.Summary: HDL regulates inflammation and CVD through a variety of mechanisms independent of reverse cholesterol transport, including autophagy, LDL deposition, endotoxin clearance.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"191-195"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705669","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 introduction. 编辑介绍。

IF 4.5 3区医学

Current opinion in lipidology Pub Date : 2026-10-01 Epub Date: 2026-09-03 DOI: 10.1097/MOL.0000000000001057

引用次数: 0

Atherosclerosis: cell biology and lipoproteins. 动脉粥样硬化：细胞生物学和脂蛋白。

IF 4.5 3区医学

Current opinion in lipidology Pub Date : 2026-10-01 Epub Date: 2026-09-03 DOI: 10.1097/MOL.0000000000001055

Mohamad Navab

引用次数: 0

Lipids in endothelial-to-mesenchymal transition. 脂质在内皮向间质转化中的作用。

IF 4.5 3区医学

Current opinion in lipidology Pub Date : 2026-10-01 Epub Date: 2026-08-12 DOI: 10.1097/MOL.0000000000001051

Christina K Tripsas, Abigail Y Tsai, Jeffrey J Hsu

引用次数: 0

Lipids and lipoproteins in calcific aortic valve disease. 钙化主动脉瓣疾病中的脂质和脂蛋白。

IF 4.5 3区医学

Current opinion in lipidology Pub Date : 2026-10-01 Epub Date: 2026-08-12 DOI: 10.1097/MOL.0000000000001053

Olcay Aksoy, Yin Tintut, Linda L Demer

{"title":"Lipids and lipoproteins in calcific aortic valve disease.","authors":"Olcay Aksoy, Yin Tintut, Linda L Demer","doi":"10.1097/MOL.0000000000001053","DOIUrl":"10.1097/MOL.0000000000001053","url":null,"abstract":"Purpose of review: Lipids and lipoproteins have established roles in calcific atherosclerosis, but there is less awareness of their role in calcific aortic valve disease (CAVD). Clinical studies link CAVD with severe hypercholesterolemia, and genetic studies consistently link it with lipoprotein little (a) [Lp(a)], a major carrier of oxidized phospholipids. Given the remarkable similarities between calcific atherosclerotic plaques and calcific aortic valves, lipids are incriminated. Hence, lipid-lowering therapies used for atherosclerosis have been tested in CAVD, but results have been inexplicably disappointing. New evidence for the importance of lipids, despite failure of lipid-lowering, and new concepts in diagnostic and therapeutic approaches are discussed.Recent findings: Evidence supports a key role of Lp(a) levels in CAVD. Potential diagnostic advances include pH-sensitive-fluorescence probes for visualizing lipid droplets in valves and identification of natural antibodies to modified LDL that associate inversely with CAVD. Potential therapeutic advances include Lp(a) lowering, SGLT2 inhibition, and reactivation of soluble guanylate cyclase. Trial outcomes currently remain mixed.Summary: Recent studies clarify the mechanisms by which lipids, lipoproteins, and Lp(a) contribute to CAVD. New potential diagnostic techniques include screening for natural antibodies and visualizing lipid deposits. New therapeutic agents include oligonucleotides and nanoparticles. New clinical trials are underway.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"185-190"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720542","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): a unique lipoprotein at the crossroads of atherosclerosis and thrombosis. 脂蛋白(a)：一种独特的脂蛋白，处于动脉粥样硬化和血栓形成的十字路口。

IF 4.5 3区医学

Current opinion in lipidology Pub Date : 2026-10-01 Epub Date: 2026-08-05 DOI: 10.1097/MOL.0000000000001049

Michael B Boffa, Marlys L Koschinsky

{"title":"Lipoprotein(a): a unique lipoprotein at the crossroads of atherosclerosis and thrombosis.","authors":"Michael B Boffa, Marlys L Koschinsky","doi":"10.1097/MOL.0000000000001049","DOIUrl":"10.1097/MOL.0000000000001049","url":null,"abstract":"Purpose of review: Elevated plasma concentrations of lipoprotein(a) [Lp(a)] are a causal and independent risk factor for atherosclerotic cardiovascular disease and an emerging therapeutic target. However, despite Lp(a) being on the cusp of widespread clinical consideration, fundamental questions regarding the pathophysiology of Lp(a) remain, most notably its contribution to atherothrombosis. This review will summarize recent evidence for both indirect and direct prothrombotic roles of Lp(a).Recent findings: Preclinical studies show that the proinflammatory properties of Lp(a) - largely attributable to its cargo of oxidized phospholipids - promote vulnerable plaques through effects on vascular and immune/inflammatory cells. Advanced imaging techniques show that elevated Lp(a) is associated with vulnerable plaque phenotypes in patients. Regarding thrombosis, previous assumptions that Lp(a) is antifibrinolytic have given way to an emerging picture that Lp(a) promotes a lysis-resistant clot architecture while stimulating the coagulation cascade and potentiating platelet responses. Indeed, clinical studies have demonstrated that patients with elevated Lp(a) specifically accrue clinical benefit from aspirin in the primary prevention setting.Summary: That elevated Lp(a) is both directly and indirectly prothrombotic remains to be proven by additional clinical and animal model studies Nonetheless, the accumulating evidence indicates that considering the prothrombotic activities of Lp(a) will impact clinical management of Lp(a) and the deployment of Lp(a)-lowering therapies.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"211-217"},"PeriodicalIF":4.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812458","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

Current, novel and emerging lipid-lowering therapies in pediatric familial hypercholesterolemia. 目前，新的和新兴的降脂疗法在儿童家族性高胆固醇血症。

IF 4.5 3区医学

Current opinion in lipidology Pub Date : 2026-09-19 DOI: 10.1097/MOL.0000000000001060

Eelke Houter, Sibbeliene E van den Bosch, Barbara A Hutten, Willemijn E Corpeleijn

{"title":"Current, novel and emerging lipid-lowering therapies in pediatric familial hypercholesterolemia.","authors":"Eelke Houter, Sibbeliene E van den Bosch, Barbara A Hutten, Willemijn E Corpeleijn","doi":"10.1097/MOL.0000000000001060","DOIUrl":"https://doi.org/10.1097/MOL.0000000000001060","url":null,"abstract":"Purpose of review: Over the past decade, pharmacological treatment options for children with familial hypercholesterolemia (FH) have expanded considerably. The recent European Atherosclerosis Society consensus recommends more stringent LDL cholesterol (LDL-C) targets than previously advocated. Consequently, more children with FH are expected to become eligible for novel therapeutic options. This review summarizes established and emerging lipid-lowering therapies (LLT) evaluated in children, focusing on recent and ongoing clinical trials.Recent findings: Conventional LLT remains the cornerstone of FH treatment, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are approved for pediatric use and achieve significant LDL-C reductions; however, injectable administration and high costs limit their widespread use. Novel oral PCSK9 inhibitors are currently under investigation in clinical trials, and fixed-dose combinations may offer a more practical and cost-effective approach. Additionally, angiopoietin-like protein 3 inhibitors and microsomal triglyceride transfer protein inhibitors lower LDL-C in dependently of LDL receptor activity, making them particularly suitable for homozygous FH patients.Summary: The management of FH is entering a new therapeutic era. As therapeutic options expand and agents with greater LDL-C reductions become available, personalized treatment strategies will become increasingly important to achieve LDL-C targets and may ultimately shift from stepwise intensification approaches toward early intensive treatment.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001368","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