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Genetic testing for familial hypercholesterolemia. 家族性高胆固醇血症基因检测。
IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-04-01 Epub Date: 2024-01-31 DOI: 10.1097/MOL.0000000000000925
Yiyi Zhang, Sarah D de Ferranti, Andrew E Moran

Purpose of review: Despite familial hypercholesterolemia (FH) being the most common genetic cause of cardiovascular disease (CVD), genetic testing is rarely utilized in the US. This review summarizes what is known about the clinical utility of genetic testing and its role in the diagnosis and screening of FH.

Recent findings: The presence of an FH-causative variant is associated with a substantially higher risk of CVD, even when low-density lipoprotein cholesterol (LDL-C) levels are only modestly elevated. Genetic testing can facilitate the identification of FH cases who may be missed by clinical diagnostic criteria, improve risk stratification beyond LDL-C and family history, guide treatment decisions, and improve treatment initiation and adherence. Genetic testing can be incorporated into FH screening and diagnosis algorithms, including cascade, targeted, and universal screening. Integrating genetic testing into cascade screening can enhance the effectiveness of the process. Several models of universal FH screening with coordinated genetic and lipid testing are feasible and effective.

Summary: More systematic integration of genetic testing into FH diagnosis and screening can significantly reduce the burden of this condition through early detection and treatment. Further pragmatic implementation studies are needed to determine how to more effectively and affordably integrate genetic testing into clinical lipid screening programs.

综述目的:尽管家族性高胆固醇血症(FH)是心血管疾病(CVD)最常见的遗传病因,但在美国却很少使用基因检测。本综述总结了基因检测的临床实用性及其在诊断和筛查家族性高胆固醇血症中的作用:即使低密度脂蛋白胆固醇(LDL-C)水平仅略有升高,FH 致病变体的存在也与心血管疾病风险的大幅升高有关。基因检测有助于发现临床诊断标准可能遗漏的 FH 病例,改善低密度脂蛋白胆固醇和家族史之外的风险分层,指导治疗决策,并改善治疗的启动和坚持性。基因检测可纳入 FH 筛查和诊断算法,包括级联筛查、靶向筛查和普遍筛查。将基因检测纳入级联筛查可提高筛查的有效性。总结:将基因检测更系统地纳入 FH 诊断和筛查,可通过早期检测和治疗大大减轻该疾病的负担。需要进一步开展务实的实施研究,以确定如何更有效、更经济地将基因检测纳入临床血脂筛查计划。
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引用次数: 0
Novel functions of Tribbles-homolog 1 in liver, adipocytes and atherosclerosis. Tribbles-homolog 1 在肝脏、脂肪细胞和动脉粥样硬化中的新功能。
IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-04-01 Epub Date: 2024-01-17 DOI: 10.1097/MOL.0000000000000917
Ileana Hernandez-Resendiz, Ralph Burkhardt

Purpose of review: Human genetics studies have sparked great interest in the pseudokinase Tribbles homolog 1, as variant at the TRIB1 gene locus were robustly linked to several cardiometabolic traits, including plasma lipids and coronary artery disease. In this review, we summarize recent findings from mouse models that investigated the function of hepatic and adipocyte Trib1 in lipid metabolism and its role in atherosclerosis.

Recent findings: Studies in atherosclerosis prone low-density lipoprotein (LDL)-receptor knockout mice suggested that systemic Trib1 -deficiency promotes atherosclerotic lesion formation through the modulation of plasma lipids and inflammation. Further, investigations in mice with hepatocyte specific deletion of Trib1 identified a novel role in the catabolism of apoB-containing lipoproteins via regulation of the LDL-receptor. Moreover, recent studies on Trib1 in adipocytes uncovered critical functions in adipose tissue biology, including the regulation of plasma lipid and adiponectin levels and the response to β3-adrenergic receptor activation.

Summary: Functional studies in mice have expanded our understanding of how Trib1 contributes to various aspects of cardiometabolic diseases. They support the notion that Trib1 exerts tissue-specific effects, which can result in opposing effects on cardiometabolic traits. Additional studies are required to fully elucidate the molecular mechanisms underlying the cellular and systemic effects of Trib1 .

综述目的:人类遗传学研究引发了人们对假性激酶Tribbles同源物1的极大兴趣,因为TRIB1基因位点的变异与多种心脏代谢特征(包括血浆脂质和冠状动脉疾病)密切相关。在这篇综述中,我们总结了小鼠模型中研究肝脏和脂肪细胞 Trib1 在脂质代谢中的功能及其在动脉粥样硬化中作用的最新发现:对易发生动脉粥样硬化的低密度脂蛋白(LDL)受体敲除小鼠的研究表明,全身性Trib1缺陷通过调节血浆脂质和炎症促进动脉粥样硬化病变的形成。此外,在肝细胞特异性缺失 Trib1 的小鼠中进行的研究发现,Trib1 通过调节低密度脂蛋白受体,在含载脂蛋白 B 的脂蛋白分解代谢中发挥了新的作用。此外,最近对脂肪细胞中 Trib1 的研究发现了其在脂肪组织生物学中的关键功能,包括调节血浆脂质和脂肪连蛋白水平以及对β3-肾上腺素能受体激活的反应:小鼠功能研究拓展了我们对 Trib1 如何促进心脏代谢疾病各个方面的认识。这些研究支持这样一种观点,即 Trib1 可发挥组织特异性效应,从而对心脏代谢特征产生相反的影响。要全面阐明 Trib1 的细胞和系统效应的分子机制,还需要进行更多的研究。
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引用次数: 0
High-density lipoprotein functionality, cardiovascular health, and patterns of alcohol consumption: new insights and future perspectives. 高密度脂蛋白功能、心血管健康和饮酒模式:新见解和未来展望。
IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-10-03 DOI: 10.1097/MOL.0000000000000906
Marta Trius-Soler, Kenneth J Mukamal, Marta Guasch-Ferré

Purpose of review: Cardiovascular diseases (CVD) pose a significant public health challenge, contributing to 422 million disability-adjusted life years in 2021. The role of high-density lipoproteins (HDL) and alcohol consumption, one of their major modifiable determinants, remains controversial. The objective of this review is to provide a comprehensive narrative overview of HDL functionality and its predictive value for CVD in relation to patterns of alcohol consumption.

Recent findings: HDL phenotypes beyond HDL-cholesterol (HDL-c) such as distribution of HDL subspecies, HDL particle abundance, and reverse cholesterol transport capacity are promising indicators of atherosclerotic CVD risk. Low-to-moderate alcohol consumption seems to improve HDL functionality and reduce the incidence of CVD among primarily middle-aged men and postmenopausal women. Advancements in our understanding of HDL biogenesis, structure, and function hold promise for improving HDL-related measures and their predictive value for cardiovascular health.

Summary: Low-to-moderate alcohol consumption appears to not only increase HDL-c concentration found in the HDL fraction of plasma but also enhance HDL functionality, providing insights into the underlying mechanisms linking alcohol exposure and cardiovascular health benefits. However, rigorous, well designed intervention trials of alcohol consumption on hard cardiovascular outcomes are needed to identify robust causal associations of HDL phenotypes and alcohol consumption with cardiovascular risk.

综述目的:心血管疾病(CVD)是一项重大的公共卫生挑战,2021年导致4.22亿残疾调整寿命。高密度脂蛋白(HDL)和饮酒(其主要可改变的决定因素之一)的作用仍然存在争议。本综述的目的是提供高密度脂蛋白功能及其与饮酒模式相关的心血管疾病预测价值的全面综述。最近的发现:HDL-c以外的HDL表型,如HDL亚群的分布、HDL颗粒丰度和反向胆固醇转运能力,是动脉粥样硬化CVD风险的有希望的指标。在中年男性和绝经后女性中,低至中度饮酒似乎可以改善高密度脂蛋白功能,降低心血管疾病的发病率。我们对高密度脂蛋白生物发生、结构和功能的理解的进步有望改善高密度脂素相关指标及其对心血管健康的预测价值。摘要:低至中度饮酒似乎不仅会增加血浆中HDL-c的浓度,还会增强HDL的功能,从而深入了解酒精暴露与心血管健康益处之间的潜在机制。然而,需要对饮酒对心血管硬后果的干预试验进行严格、精心设计,以确定高密度脂蛋白表型和饮酒与心血管风险之间的有力因果关系。
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引用次数: 0
Cardiovascular disease prevention in heterozygous familial hypercholesterolemia: how important is a healthy diet in the era of long-lasting cholesterol-lowering drug therapies? 杂合性家族性高胆固醇血症的心血管疾病预防:在长期降胆固醇药物治疗的时代,健康饮食有多重要?
IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-11-01 DOI: 10.1097/MOL.0000000000000908
Gabrielle Roy, Jean-Philippe Drouin-Chartier

Purpose of review: This review aims to provide an in-depth perspective on the importance of diet for cardiovascular disease (CVD) prevention in heterozygous familial hypercholesterolemia (HeFH).

Recent findings: Even though data on diet and CVD prevention in HeFH are limited, the currently available evidence supports its cholesterol-lowering effect and its favorable association with CVD risk on the long-term. However, qualitative evidence from individuals with HeFH suggests that there is a common perception that diet is useless compared to medication, and this misconception serves as a barrier to healthy eating. On the other hand, evidence also suggests that individuals with HeFH are at higher risk of eating disorders compared with unaffected individuals. Family history of premature death and the chronic nature of the disease would be in cause.

Summary: Emphasizing a healthy diet needs to remain at the foundation of CVD prevention in HeFH. Evidence are limited but supportive of the cholesterol-lowering and cardioprotective potential effects of diet. Engaging in conversations about healthy dieting with individuals in HeFH is likely to help prevent misconceptions about diet. Additionally, it could help reduce the risk of eating disorders, which, altogether, is likely to improve overall CVD prevention.

综述目的:本综述旨在深入探讨饮食对杂合子家族性高胆固醇血症(HeFH)心血管疾病(CVD)预防的重要性。最近的研究结果:尽管关于HeFH饮食和CVD预防的数据有限,目前可用的证据支持其降低胆固醇的作用及其与心血管疾病风险的长期有利关联。然而,来自HeFH患者的定性证据表明,人们普遍认为饮食与药物相比毫无用处,这种误解是健康饮食的障碍。另一方面,有证据表明,与未受影响的个体相比,患有HeFH的个体患饮食失调的风险更高。过早死亡的家族史和这种疾病的慢性性质可能是病因。总结:强调健康饮食仍然是预防脑脊髓炎心血管疾病的基础。证据有限,但支持饮食降低胆固醇和心脏保护的潜在作用。与HeFH中的个人进行关于健康节食的对话可能有助于防止对饮食的误解。此外,它可以帮助降低饮食失调的风险,这可能会提高心血管疾病的整体预防。
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引用次数: 0
Lipidome and inflammation interplay: the role of diet in this relationship. 脂质和炎症的相互作用:饮食在这种关系中的作用。
IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-11-08 DOI: 10.1097/MOL.0000000000000909
Anacristina Rovayo, Estefanía Toledo, Cristina Razquin

Purpose of review: The aim of this review was to provide an overview of the role of novel lipid biomarkers from the circulating lipidome in inflammatory processes and the impact that dietary patterns may have on the lipidome.

Recent findings: Inflammation is a process that underlies many acute and chronic diseases, contributing to their development and severity. Finding novel molecules which serve as biomarkers and which are involved in inflammation is very useful, since they offer us both preventive or therapeutic targets and reveal mechanisms of action. Recently, several studies have found circulating lipid molecules that are implicated in inflammatory processes of different diseases, such as cardiovascular diseases, type 2 diabetes, COVID-19 or other respiratory infectious diseases. As such, ceramides, triacylglicerides or lysophosphatidylcholines have been associated with inflammation in a different manner depending on the stage of inflammation. The study of dietary patterns, especially healthy ones as the Mediterranean or the Nordic diets, has shown the impact that dietary habits may have on the lipidomic profile of individuals.

Conclusions: Healthy dietary patterns have been suggested to exert beneficial effects in the circulating lipid profile. Studying the circulating lipidome could help to find new biomarkers of underlying inflammation, especially in cases of chronic low-grade inflammatory diseases in which it is more difficult to detect.

目的:本综述的目的是概述循环脂质中新的脂质生物标志物在炎症过程中的作用,以及饮食模式可能对脂质产生的影响。最近的发现:炎症是许多急性和慢性疾病的基础,导致其发展和严重程度。寻找作为生物标志物并参与炎症的新分子是非常有用的,因为它们为我们提供了预防或治疗靶点,并揭示了作用机制。最近,几项研究发现,循环脂质分子与不同疾病的炎症过程有关,如心血管疾病、2型糖尿病、新冠肺炎或其他呼吸道传染病。因此,神经酰胺、三酰甘油醚或溶血磷脂酰胆碱根据炎症阶段以不同的方式与炎症相关。对饮食模式的研究,特别是对地中海或北欧等健康饮食模式的调查,表明了饮食习惯可能对个体的脂质组学特征产生的影响。结论:健康的饮食模式已被建议对循环脂质状况发挥有益作用。研究循环脂质可以帮助寻找潜在炎症的新生物标志物,特别是在更难检测的慢性低度炎症疾病的情况下。
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引用次数: 0
Dietary fat, telomere length and cognitive function: unravelling the complex relations. 膳食脂肪、端粒长度与认知功能:揭开复杂关系。
IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-11-29 DOI: 10.1097/MOL.0000000000000900
Hamza Mostafa, Laia Gutierrez-Tordera, Javier Mateu-Fabregat, Christopher Papandreou, Mònica Bulló

Purpose of review: The review aims to explore the recent evidence on the associations between different dietary fat intake and cognitive function, and to understand the role of telomere length in this relationship.

Recent findings: Clinical and preclinical studies included in this review suggest that dietary fat intake is associated with cognitive function and telomere length. High intake of saturated fats and trans fats, commonly found in ultra-processed foods, appears to have negative effects on cognitive function and telomere length, while other dietary fats, such as omega-3 polyunsaturated fatty acids and monounsaturated fatty acids are associated with improved cognitive performance and reduced telomere attrition. Controversial results related to omega-6 polyunsaturated fatty acids intake and its impact on cognitive function were found. Dietary fats may affect telomere length and cognition through oxidative stress, inflammation, and insulin resistance.

Summary: The current review illustrated the relationship between dietary fat and cognitive function by focusing on the role of telomere length as a potential intermediator. More future studies are required, however, in order to develop targeted interventions aimed at preserving cognitive well-being throughout life.

综述目的:本综述旨在探讨不同膳食脂肪摄入量与认知功能之间关系的最新证据,并了解端粒长度在这一关系中的作用。最新发现:本综述中包括的临床和临床前研究表明,膳食脂肪摄入量与认知功能和端粒长度有关。过量摄入超加工食品中常见的饱和脂肪和反式脂肪,似乎对认知功能和端粒长度有负面影响,而其他膳食脂肪,如omega-3多不饱和脂肪酸和单不饱和脂肪酸,则与提高认知能力和减少端粒损耗有关。发现了有关摄入omega-6多不饱和脂肪酸及其对认知功能影响的有争议的结果。膳食脂肪可能通过氧化应激、炎症和胰岛素抵抗影响端粒长度和认知。摘要:目前的综述通过关注端粒长度作为潜在中介的作用来说明膳食脂肪与认知功能之间的关系。然而,为了开发有针对性的干预措施,以保持一生的认知健康,还需要更多的未来研究。
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引用次数: 0
Pregnancy, cardiovascular health, and microchimerism. 怀孕、心血管健康和微嵌合。
IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-11-20 DOI: 10.1097/MOL.0000000000000914
Sara Hallum Søndergaard, Mads Kamper-Jørgensen

Purpose of review: To provide an updated review of scientific literature concerning associations between pregnancy and cardiovascular health among women, and to discuss a possible impact of microchimerism on the association.

Recent findings: In most studies, pregnancy and childbirth is associated with increased risk of cardiovascular disease in women. Some ascribe the association mainly to lifestyle, whereas others suggest that pregnancy itself negatively affects women's cardiovascular health. Pregnancy is a natural source of microchimerism, which in turn markedly affects female health. The only study published in the area surprisingly shows that among middle-aged women, male-origin microchimerism (MOM) is associated with half the risk of developing ischemic heart disease (IHD). No similar association is found between MOM and ischemic stroke.

Summary: The sparse evidence published suggests reduced risk of developing IHD among MOM-positive women. Despite the association being biologically plausible, replication of the findings is warranted to support that this is not a chance finding.

综述的目的:提供有关怀孕与女性心血管健康之间关系的科学文献的最新综述,并讨论微嵌合在这种关系中的可能影响。最新发现:在大多数研究中,怀孕和分娩与女性患心血管疾病的风险增加有关。一些人将这种联系主要归因于生活方式,而另一些人则认为怀孕本身会对女性的心血管健康产生负面影响。怀孕是微嵌合的自然来源,这反过来又显著影响女性的健康。在该领域发表的唯一一项令人惊讶的研究表明,在中年妇女中,男性来源的微嵌合(MOM)与患缺血性心脏病(IHD)的风险有一半相关。在MOM和缺血性中风之间没有发现类似的关联。摘要:已发表的少量证据表明,妈妈阳性妇女患IHD的风险降低。尽管这种联系在生物学上是合理的,但研究结果的重复证明,这不是一个偶然的发现。
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引用次数: 0
Circulating cell-free DNA and its association with cardiovascular disease: what we know and future perspectives. 循环无细胞DNA及其与心血管疾病的关系:我们所知道的和未来的展望。
IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-10-06 DOI: 10.1097/MOL.0000000000000907
Steffen Ullitz Thorsen, Kristine Frøsig Moseholm, Frederik Banch Clausen

Purpose of review: The aim of this review is to explore a possible link between cell-free DNA (cfDNA) and cardiovascular disease (CVD), which may hold valuable potential for future diagnostics.

Recent findings: cfDNA has become topic of high interest across several medical fields. cfDNA is used as a diagnostic biomarker in cancer, prenatal care, and transplantation. In addition, cfDNA may play an unrecognized role in biological processes that are involved in or underlying various disease states, for example, inflammation. Elevated levels of cfDNA are associated with various elements of CVD, cardio-metabolic risk factors, and autoimmune diseases. Mitochondrial cfDNA and neutrophil extracellular traps may play distinct roles. Total circulating cfDNA may reflect the unspecific accumulation of stressors and the organism's susceptibility and resilience to such stressors. As such, cfDNA, in a stressful situation, may provide predictive value for future development of CVD. We suggest exploring such possibility through a large-scale prospective cohort study of pregnant women.

Summary: There is no doubt that cfDNA is a valuable biomarker. For CVD, its potential is indicated but less explored. New studies may identify cfDNA as a valuable circulating cardiovascular risk marker to help improve risk stratification.

综述目的:本综述的目的是探索无细胞DNA(cfDNA)与心血管疾病(CVD)之间的可能联系,这可能对未来的诊断具有宝贵的潜力。最近的发现:cfDNA已经成为多个医学领域高度关注的话题。cfDNA被用作癌症、产前护理和移植的诊断生物标志物。此外,cfDNA可能在参与或潜在的各种疾病状态(例如炎症)的生物过程中发挥未被认识的作用。cfDNA水平升高与心血管疾病、心脏代谢危险因素和自身免疫性疾病的各种因素有关。线粒体cfDNA和中性粒细胞外陷阱可能发挥不同的作用。总循环cfDNA可能反映应激源的非特异性积累以及生物体对这些应激源的易感性和恢复力。因此,在紧张的情况下,cfDNA可能为CVD的未来发展提供预测价值。我们建议通过对孕妇进行大规模前瞻性队列研究来探索这种可能性。摘要:毫无疑问,cfDNA是一种有价值的生物标志物。对于CVD,其潜力已被指出,但探索较少。新的研究可能会确定cfDNA是一种有价值的循环心血管风险标志物,有助于改善风险分层。
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引用次数: 0
Editorial introductions. 编辑介绍。
IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-12-20 DOI: 10.1097/MOL.0000000000000912
{"title":"Editorial introductions.","authors":"","doi":"10.1097/MOL.0000000000000912","DOIUrl":"https://doi.org/10.1097/MOL.0000000000000912","url":null,"abstract":"","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":"35 1","pages":"v-vi"},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138800350","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
Genetic variation in apolipoprotein A-V in hypertriglyceridemia. 高甘油三酯血症中载脂蛋白 A-V 的遗传变异。
IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-21 DOI: 10.1097/mol.0000000000000916
Shehan D Perera, Robert A Hegele
While biallelic rare APOA5 pathogenic loss-of-function (LOF) variants cause familial chylomicronemia syndrome, heterozygosity for such variants is associated with highly variable triglyceride phenotypes ranging from normal to severe hypertriglyceridemia, often in the same individual at different time points. Here we provide an updated overview of rare APOA5 variants in hypertriglyceridemia.
虽然双拷贝罕见 APOA5 致病性功能缺失(LOF)变体会导致家族性乳糜微粒血症综合征,但此类变体的杂合性与甘油三酯表型的高度可变性有关,从正常到严重的高甘油三酯血症不等,通常在不同时间点出现在同一个人身上。在此,我们提供了有关高甘油三酯血症中罕见 APOA5 变异的最新概述。
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引用次数: 0
期刊
Current opinion in lipidology
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