Current opinion in lipidology最新文献_第3页

The emerging role of fat-inducing transcript 2 in endoplasmic reticulum proteostasis and lipoprotein biogenesis. 脂肪诱导转录本 2 在内质网蛋白稳态和脂蛋白生物生成过程中的新作用。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-10-01 Epub Date: 2024-08-22 DOI: 10.1097/MOL.0000000000000943

Jeffrey L Brodsky, Anuradha Iyer, Konstantinos I Fortounas, Edward A Fisher

{"title":"The emerging role of fat-inducing transcript 2 in endoplasmic reticulum proteostasis and lipoprotein biogenesis.","authors":"Jeffrey L Brodsky, Anuradha Iyer, Konstantinos I Fortounas, Edward A Fisher","doi":"10.1097/MOL.0000000000000943","DOIUrl":"10.1097/MOL.0000000000000943","url":null,"abstract":"Purpose of review: This review examines the evolving role of the fat-inducing transcript 2 (FIT2) protein in lipid droplet (LD) biology and its broader implications in cellular physiology and disease. With recent advancements in understanding FIT2 function across various model systems, this review provides a timely synthesis of its mechanisms and physiological significance.Recent findings: FIT2, an endoplasmic reticulum (ER)-resident protein, has been established as a critical regulator of LD formation in diverse organisms, from yeast to mammals. It facilitates LD biogenesis by sequestering diacylglycerol (DAG) and potentially influencing ER membrane dynamics. Beyond its role in lipid metabolism, FIT2 intersects with the ER-associated degradation (ERAD), is critical for protein homeostasis, and is linked to the unfolded protein response (UPR). Dysregulation of FIT2 has also been linked to metabolic disorders such as insulin resistance and lipodystrophy, highlighting its clinical relevance.Summary: Insights into FIT2 function underscore its pivotal role in LD formation and lipid homeostasis. Understanding its involvement in ER proteostasis and very low density lipoprotein biogenesis has broad implications for metabolic diseases and cancer. Therapeutic strategies targeting FIT2 may offer novel approaches to modulate lipid metabolism and mitigate associated pathologies. Further research is needed to elucidate the full spectrum of FIT2's interactions within cellular lipid and protein networks, potentially uncovering new therapeutic avenues for metabolic and ER stress-related disorders.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"248-252"},"PeriodicalIF":3.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035518","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

Proprotein convertase subtilisin/kexin type 9 as a drug target for abdominal aortic aneurysm. 作为治疗腹主动脉瘤药物靶点的 Proprotein convertase subtilisin/kexin type 9。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-10-01 Epub Date: 2024-07-22 DOI: 10.1097/MOL.0000000000000945

Jonathan Golledge, Hong S Lu, Sonia Shah

{"title":"Proprotein convertase subtilisin/kexin type 9 as a drug target for abdominal aortic aneurysm.","authors":"Jonathan Golledge, Hong S Lu, Sonia Shah","doi":"10.1097/MOL.0000000000000945","DOIUrl":"10.1097/MOL.0000000000000945","url":null,"abstract":"Purpose of review: There are no current drug therapies to limit abdominal aortic aneurysm (AAA) growth. This review summarizes evidence suggesting that inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) may be a drug target to limit AAA growth.Recent findings: Mendelian randomization studies suggest that raised LDL and non-HDL-cholesterol are causal in AAA formation. PCSK9 was reported to be upregulated in human AAA samples compared to aortic samples from organ donors. PCSK9 gain of function viral vectors promoted aortic expansion in C57BL/6 mice infused with angiotensin II. The effect of altering PCSK9 expression in the aortic perfusion elastase model was reported to be inconsistent. Mutations in the gene encoding PCSK9, which increase serum cholesterol, were associated with increased risk of human AAA. Patients with AAA also have a high risk of cardiovascular death, myocardial infarction and stroke. Recent research suggests that PCSK9 inhibition would substantially reduce the risk of these events.Summary: Past research suggests that drugs that inhibit PCSK9 have potential as a novel therapy for AAA to both limit aneurysm growth and reduce risk of cardiovascular events. A large multinational randomized controlled trial is needed to test if PCSK9 inhibition limits AAA growth and cardiovascular events.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"241-247"},"PeriodicalIF":3.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757727","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

Strategies for management of patients with elevated lipoprotein(a). 脂蛋白（a）升高患者的管理策略。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-10-01 Epub Date: 2024-08-14 DOI: 10.1097/MOL.0000000000000950

Charlotte C Ellberg, Harpreet S Bhatia

{"title":"Strategies for management of patients with elevated lipoprotein(a).","authors":"Charlotte C Ellberg, Harpreet S Bhatia","doi":"10.1097/MOL.0000000000000950","DOIUrl":"10.1097/MOL.0000000000000950","url":null,"abstract":"Purpose of review: There is growing literature that supports the testing of Lp(a). However, few patients are tested, including those with a personal or family history of cardiovascular disease (CVD). One often noted barrier to more widespread testing is uncertainty regarding what to do with an elevated Lp(a) level. Although guidelines vary, there is agreement on the use of Lp(a) as a risk enhancer to guide medical care and shared decision-making. This review will discuss a clinical approach with supporting evidence for management of patients with elevated Lp(a).Recent findings: At the minimum, elevated Lp(a) increases cardiovascular risk and can be incorporated into existing risk stratification paradigms. The cornerstone of management is aggressive management of traditional cardiovascular risk factors, including LDL-cholesterol (LDL-C). More recent studies have highlighted the potential role for proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), aspirin in primary prevention, and prolonged dual antiplatelet therapy in secondary prevention.Summary: Although there is optimism for Lp(a)-targeted therapies in the near future, an elevated Lp(a) level is actionable today, and uncertainty regarding the management of patients with elevated Lp(a) should not be a barrier to more widespread testing.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"234-240"},"PeriodicalIF":3.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11387124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981969","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

Effectiveness of cascade screening for elevated lipoprotein(a), an underdiagnosed family disorder. 对脂蛋白（a）升高（一种诊断不足的家族性疾病）进行级联筛查的效果。

IF 4.4 3区医学

Current opinion in lipidology Pub Date : 2024-08-27 DOI: 10.1097/mol.0000000000000951

Maxim E Annink,Emma S Janssen,Laurens F Reeskamp

{"title":"Effectiveness of cascade screening for elevated lipoprotein(a), an underdiagnosed family disorder.","authors":"Maxim E Annink,Emma S Janssen,Laurens F Reeskamp","doi":"10.1097/mol.0000000000000951","DOIUrl":"https://doi.org/10.1097/mol.0000000000000951","url":null,"abstract":"PURPOSE OF REVIEWElevated lipoprotein(a) [Lp(a)] is a prevalent, independent, genetic risk factor for cardiovascular disease. Though crucial for adequate risk assessment, detection of individuals at increased risk because of elevated Lp(a) is severely lacking in practice. In this light, several consensus statements have recommended familial cascade screening strategies to increase detection of elevated Lp(a). This review aims to synthesize findings from recent research into the effectiveness of cascade screening for elevated Lp(a).RECENT FINDINGSCascade screening is an effective method for identifying individuals with elevated Lp(a) and is superior to opportunistic screening. Cascade screening identifies approximately one new case of elevated Lp(a) ≥ 125 nmol/L for every two first-degree relatives screened. The number needed to screen (NNS) ranged from 1.3 to 2.9, depending on Lp(a) threshold values and selected population.SUMMARYCascade screening appears to be a promising strategy for identifying individuals with elevated Lp(a). However, several challenges persist regarding the implementation of this strategy in clinical practice. Deciding on threshold values for initiating cascade screening, considering the implications of ethnicity-related variability of Lp(a) levels, and further research into the clinical relevance of cascade screening are crucial steps. Understanding these factors will be essential for optimizing cascade screening protocols and enhancing its effectiveness in clinical practice.GRAPHICAL ABSTRACThttp://links.lww.com/COL/A31.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":"8 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206235","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

How safe are proprotein convertase subtilisinekexin type 9 inhibitors in diabetes? 糖尿病患者使用 9 型蛋白转化酶枯草酶抑制剂的安全性如何？

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-08-01 Epub Date: 2024-03-19 DOI: 10.1097/MOL.0000000000000934

Tian Chen, Naifeng Liu

{"title":"How safe are proprotein convertase subtilisinekexin type 9 inhibitors in diabetes?","authors":"Tian Chen, Naifeng Liu","doi":"10.1097/MOL.0000000000000934","DOIUrl":"10.1097/MOL.0000000000000934","url":null,"abstract":"Purpose of review: To examine the safety of proprotein convertase subtilisinekexin type 9 (PCSK9) inhibitors in patients with diabetes, specifically focusing on their impact on glucose metabolism.Recent findings: Patients with diabetes often require intensified lipid-lowering therapy. PCSK9 inhibitors can reduce low-density lipoprotein cholesterol (LDL-C) concentrations by approximately 60%, and significantly reduce cardiovascular risk when added to statin therapy. Some studies have suggested an association between low LDL-C levels and an increased risk of new-onset diabetes, and genetics has almost consistently shown an increased glucose concentration and risk of diabetes. Most clinical trials have not demonstrated a deterioration in glycaemic control in patients with diabetes after the use of PCSK9 inhibitors, and they do not lead to other significant treatment-emergent adverse events.Summary: Although the majority of patients with diabetes are undergoing background statin therapy, which may mask potential adverse effects of PCSK9 inhibitors on glycaemic control, current data suggest that the benefits outweigh the risks for diabetic patients using PCSK9 inhibitors. Considering the different nature of genetic studies and of clinical trials, close monitoring of glucose parameters is necessary, especially in individuals with prediabetes.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"187-194"},"PeriodicalIF":3.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287162","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

Pancreatic and cardiometabolic complications of severe hypertriglyceridaemia. 严重高甘油三酯血症的胰腺和心脏代谢并发症。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-08-01 Epub Date: 2024-06-06 DOI: 10.1097/MOL.0000000000000939

Bilal Bashir, Maryam Ferdousi, Paul Durrington, Handrean Soran

{"title":"Pancreatic and cardiometabolic complications of severe hypertriglyceridaemia.","authors":"Bilal Bashir, Maryam Ferdousi, Paul Durrington, Handrean Soran","doi":"10.1097/MOL.0000000000000939","DOIUrl":"10.1097/MOL.0000000000000939","url":null,"abstract":"Purpose of review: This review endeavours to explore the aetiopathogenesis and impact of severe hypertriglyceridemia (SHTG) and chylomicronaemia on cardiovascular, and pancreatic complications and summarizes the novel pharmacological options for management.Recent findings: SHTG, although rare, presents significant diagnostic and therapeutic challenges. Familial chylomicronaemia syndrome (FCS), is the rare monogenic form of SHTG, associated with increased acute pancreatitis (AP) risk, whereas relatively common multifactorial chylomicronaemia syndrome (MCS) leans more towards cardiovascular complications. Despite the introduction and validation of the FCS Score, FCS continues to be underdiagnosed and diagnosis is often delayed. Longitudinal data on disease progression remains scant. SHTG-induced AP remains a life-threatening concern, with conservative treatment as the cornerstone while blood purification techniques offer limited additional benefit. Conventional lipid-lowering medications exhibit minimal efficacy, underscoring the growing interest in novel therapeutic avenues, that is, antisense oligonucleotides (ASO) and short interfering RNA (siRNA) targeting apolipoprotein C3 (ApoC3) and angiopoietin-like protein 3 and/or 8 (ANGPTL3/8).Summary: Despite advancements in understanding the genetic basis and pathogenesis of SHTG, diagnostic and therapeutic challenges persist. The rarity of FCS and the heterogenous phenotype of MCS underscore the need for the development of predictive models for complications and tailored personalized treatment strategies. The establishment of national and international registries is advocated to augment disease comprehension and identify high-risk individuals.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"208-218"},"PeriodicalIF":3.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11224574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260998","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

Proprotein convertase subtilisin/kexin type 9-inhibition across different patient populations. 不同患者群体中的 9 型枯草蛋白酶/kexin 抑制剂。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-08-01 Epub Date: 2024-03-27 DOI: 10.1097/MOL.0000000000000935

Paulina Elena Stürzebecher, Ulrich Laufs

{"title":"Proprotein convertase subtilisin/kexin type 9-inhibition across different patient populations.","authors":"Paulina Elena Stürzebecher, Ulrich Laufs","doi":"10.1097/MOL.0000000000000935","DOIUrl":"10.1097/MOL.0000000000000935","url":null,"abstract":"Purpose of review: Monoclonal antibodies (mAb) targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) have been established in cardiovascular risk prevention. The purpose of this review is to summarize the effects of PCSK9 inhibitors across different patient populations.Recent findings: Long-term data on the use of evolocumab and alirocumab shows persisting low- density lipoprotein cholesterol (LDL-C) lowering and good tolerability. PCSK9 inhibitors are effective and safe in both sexes, in pediatric patients as well as in the elderly. Initiation of PCSK9 mAb during acute myocardial infarction is safe and leads to beneficial morphological plaque changes. The PCSK9 inhibitors evolocumab, alirocumab and inclisiran lower LDL-C in patients with heterozygous familial hypercholesterolemia (FH), while the response of patients with homozygous FH is heterogeneous. New areas of application beyond lipid lowering are currently investigated.Summary: PCSK9 inhibitors are safe, well tolerated, and effective in primary and secondary prevention in a wide range of patient populations.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"179-186"},"PeriodicalIF":3.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317986","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

Paraoxonase 1: evolution of the enzyme and of its role in protecting against atherosclerosis. 副氧合酶 1：该酶的演变及其在防止动脉粥样硬化方面的作用。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-08-01 Epub Date: 2024-06-18 DOI: 10.1097/MOL.0000000000000936

Paul Durrington, Handrean Soran

{"title":"Paraoxonase 1: evolution of the enzyme and of its role in protecting against atherosclerosis.","authors":"Paul Durrington, Handrean Soran","doi":"10.1097/MOL.0000000000000936","DOIUrl":"10.1097/MOL.0000000000000936","url":null,"abstract":"Purpose of review: To review the discoveries which led to the concept that serum paraoxonase 1 (PON1) is inversely related to atherosclerotic cardiovascular disease (ASCVD) incidence, how this association came to be regarded as causal and how such a role might have evolved.Recent findings: Animal models suggest a causal link between PON1 present on HDL and atherosclerosis. Serum PON1 activity predicts ASCVD with a similar reliability to HDL cholesterol, but at the extremes of high and low HDL cholesterol, there is discordance with PON1 being potentially more accurate. The paraoxonase gene family has its origins in the earliest life forms. Its greatest hydrolytic activity is towards lactones and organophosphates, both of which can be generated in the natural environment. It is active towards a wide range of substrates and thus its conservation may have resulted from improved survival of species facing a variety of evolutionary challenges.Summary: Protection against ASCVD is likely to be the consequence of some promiscuous activity of PON1, but nonetheless has the potential for exploitation to improve risk prediction and prevention of ASCVD.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"171-178"},"PeriodicalIF":3.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11224571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418217","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

Altered lipid metabolism and the development of metabolic-associated fatty liver disease. 脂质代谢改变与代谢相关性脂肪肝的发展。

IF 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-08-01 Epub Date: 2024-03-14 DOI: 10.1097/MOL.0000000000000933

Christy Foster, Charles A Gagnon, Ambika P Ashraf

{"title":"Altered lipid metabolism and the development of metabolic-associated fatty liver disease.","authors":"Christy Foster, Charles A Gagnon, Ambika P Ashraf","doi":"10.1097/MOL.0000000000000933","DOIUrl":"10.1097/MOL.0000000000000933","url":null,"abstract":"Purpose of review: An increasing amount of research has underscored the significant role of lipoproteins in the pathogenesis of metabolic-associated fatty liver disease (MAFLD). This comprehensive review examines the intricate relationship between lipoprotein abnormalities and the development of MAFLD.Recent findings: Atherogenic dyslipidemia seen in insulin resistance states play a significant role in initiating and exacerbating hepatic lipid accumulation. There are also specific genetic factors ( PNPLA3 , TM6SF2 , MBOAT7 , HSD17B13 , GCKR- P446L) and transcription factors (SREBP-2, FXR, and LXR9) that increase susceptibility to both lipoprotein disorders and MAFLD. Most monogenic primary lipid disorders do not cause hepatic steatosis unless accompanied by metabolic stress. Hepatic steatosis occurs in the presence of secondary systemic metabolic stress in conjunction with predisposing environmental factors that lead to insulin resistance. Identifying specific aberrant lipoprotein metabolic factors promoting hepatic fat accumulation and subsequently exacerbating steatohepatitis will shed light on potential targets for therapeutic interventions.Summary: The clinical implications of interconnection between genetic factors and an insulin resistant environment that predisposes MAFLD is many fold. Potential therapeutic strategies in preventing or mitigating MAFLD progression include lifestyle modifications, pharmacological interventions, and emerging therapies targeting aberrant lipoprotein metabolism.","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"200-207"},"PeriodicalIF":3.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131003","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 3.8 3区医学

Current opinion in lipidology Pub Date : 2024-08-01 Epub Date: 2024-07-04 DOI: 10.1097/MOL.0000000000000941

引用次数: 0