Atherosclerosis最新文献

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Remnant cholesterol, LDL cholesterol, and APOB absolute mass changes explain results of prominent and other fibrate trials 残余胆固醇、低密度脂蛋白胆固醇和 APOB 绝对质量的变化解释了突出的和其他纤维酸酯试验的结果

IF 5.3 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2024-08-15 DOI: 10.1016/j.atherosclerosis.2024.118464

Takahito Doi, Anne Langsted, Børge Nordestgaard

引用次数: 0

SMLR1 is a novel player in chylomicron metabolism SMLR1 是乳糜微粒代谢过程中的新型参与者

IF 5.3 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2024-08-15 DOI: 10.1016/j.atherosclerosis.2024.118463

Ankia Visser, Marieke Smit, Niels Kloosterhuis, Nicolette Huijkman, Mirjam Koster, Bart Van De Sluis, Jan Albert Kuivenhoven

引用次数: 0

Loss-of-function variant in the glycerol kinase gene as a cause of apparent poor response to triglyceride lowering agents in patients with severe hypertriglyceridemia 甘油激酶基因中的功能缺失变异是导致严重高甘油三酯血症患者对甘油三酯降脂药物反应不佳的原因之一

IF 5.3 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2024-08-15 DOI: 10.1016/j.atherosclerosis.2024.118460

Josiane Dufour, Miriam Larouche, Diane Brisson, Daniel Gaudet

引用次数: 0

Relation between non-alcoholic fatty liver disease and acute pancreatitis in patients with severe hypertriglyceridemia and chylomicronemia 严重高甘油三酯血症和乳糜微粒血症患者的非酒精性脂肪肝与急性胰腺炎之间的关系

IF 5.3 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2024-08-15 DOI: 10.1016/j.atherosclerosis.2024.118462

Noémie Audet-Verreault, Miriam Larouche, Laura D'Erasmo, Daniele Tramontano, Francesco Baratta, Ilenia Minicocci, Martina Carosi, Simone Bini, Alessia Di Costanzo, Diane Brisson, Daniel Gaudet, Marcello Arca

引用次数: 0

Plozasiran (ARO-APOC3), an investigational RNAI therapeutic, demonstrates profound and durable reductions in APOC-3 and triglycerides (TG) in patients with severe hypertriglyceridemia (SHTG), SHASTA-2 final results 研究性 RNAI 疗法 Plozasiran（ARO-APOC3）在严重高甘油三酯血症 (SHTG) 患者中的 APOC-3 和甘油三酯 (TG) 中显示出深远而持久的降低效果，SHASTA-2 最终结果

IF 5.3 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2024-08-15 DOI: 10.1016/j.atherosclerosis.2024.118459

Daniel Gaudet, Denes Pall, Gerald Watts, Stephen Nicholls, Robert Rosenson, Karen Modesto, Ting Chang, Stacey Melquist, Ran Fu, Ma'An Muhsin, Javier San Martin, Christie Ballantyne

引用次数: 0

Dissecting the role of apolipoprotein A5 in lipoprotein metabolism 剖析脂蛋白 A5 在脂蛋白代谢中的作用

IF 5.3 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2024-08-15 DOI: 10.1016/j.atherosclerosis.2024.118461

Anni Kumari, Anna Garbers, Anamika Biswas, Michael Ploug

引用次数: 0

Relationships between HDL subpopulation proteome and HDL function in overweight/obese people with and without coronary heart disease 患有和未患有冠心病的超重/肥胖者体内高密度脂蛋白亚群蛋白质组与高密度脂蛋白功能之间的关系

IF 4.9 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2024-08-13 DOI: 10.1016/j.atherosclerosis.2024.118565

Tomas Vaisar , Ilona Babenko , Katalin V. Horvath , Katrin Niisuke , Bela F. Asztalos

Background and aims

The structure-function relationships of high-density lipoprotein (HDL) subpopulations are not well understood. Our aim was to examine the interrelationships between HDL particle proteome and HDL functionality in subjects with and without coronary heart disease (CHD).

Methods

We isolated 5 different HDL subpopulations based on charge, size, and apolipoprotein A1 (APOA1) content from the plasma of 33 overweight/obese CHD patients and 33 age-and body mass index (BMI)-matched CHD-free subjects. We measured the relative molar concentration of HDL-associated proteins by liquid chromatography tandem mass spectrometry (LC-MS/MS) and assessed particle functionality.

Results

We quantified 110 proteins associated with the 5 APOA1-containing HDL subpopulations. The relative molar concentration of these proteins spanned five orders of magnitude. Only 10 proteins were present in >1% while 73 were present in <0.1% concentration. Only 6 of the 10 most abundant proteins were apolipoproteins. Interestingly, the largest (α-1) and the smallest (preβ-1) HDL particles contained the most diverse proteomes. The protein composition of each HDL subpopulation was altered in CHD cases as compared to controls with the most prominent differences in preβ-1 and α-1 particles. APOA2 concentration was positively correlated with preβ-1 particle functionality (ABCA1-CEC/mg APOA1 in preβ-1) (R² = 0.42, p = 0.005), while APOE concentration was inversely correlated with large-HDL particle functionality (SRBI-CEC/mg APOA1 in α-1+α-2) (R² = 0.18, p = 0.01).

Conclusions

The protein composition of the different HDL subpopulations was altered differentially in CHD patients. The functionality of the small and large HDL particles correlated with the protein content of APOA2 and APOE, respectively. Our data indicate that distinct particle subspecies and specific particle associated proteins provide new information about the role of HDL in CHD.

背景和目的高密度脂蛋白（HDL）亚群的结构-功能关系尚不十分清楚。我们从 33 名超重/肥胖的冠心病患者和 33 名年龄与体重指数（BMI）相匹配的无冠心病患者的血浆中，根据电荷、大小和载脂蛋白 A1（APOA1）含量分离出 5 种不同的高密度脂蛋白亚群。我们通过液相色谱串联质谱法（LC-MS/MS）测量了高密度脂蛋白相关蛋白质的相对摩尔浓度，并评估了颗粒的功能。这些蛋白质的相对摩尔浓度跨越了五个数量级。只有 10 种蛋白质的浓度为 1%，而 73 种蛋白质的浓度为 0.1%。在 10 种含量最高的蛋白质中，只有 6 种是脂蛋白。有趣的是，最大（α-1）和最小（preβ-1）的高密度脂蛋白颗粒所含的蛋白质组最为多样。与对照组相比，冠心病病例中每个高密度脂蛋白亚群的蛋白质组成都发生了改变，其中前β-1和α-1颗粒的差异最为显著。APOA2浓度与preβ-1颗粒功能（preβ-1中的ABCA1-CEC/mg APOA1）呈正相关（R2 = 0.42，p = 0.005），而APOE浓度与大HDL颗粒功能（α-1+α-2中的SRBI-CEC/mg APOA1）呈反相关（R2 = 0.18，p = 0.01）。高密度脂蛋白小颗粒和大颗粒的功能分别与 APOA2 和 APOE 的蛋白质含量相关。我们的数据表明，不同的颗粒亚种和特定的颗粒相关蛋白为高密度脂蛋白在冠心病中的作用提供了新的信息。

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引用次数: 0

Differences in HDL-related coronary heart disease risk between individuals with and without diabetes 糖尿病患者与非糖尿病患者之间高密度脂蛋白相关冠心病风险的差异

IF 4.9 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2024-08-10 DOI: 10.1016/j.atherosclerosis.2024.118553

Jun-Xiang Chen , Qi Lu , Tingting Geng , Yuexuan Wang , Yi Wang , Rui Li , Peng-Fei Xia , Kun-Quan Guo , Kun Yang , Wen-Wei Tong , Gang Liu , An Pan , Yun-Fei Liao

Background and aims

High-density lipoprotein (HDL) might lose atheroprotective functions in the presence of diabetes. We sought to examine associations of HDL cholesterol (HDL-C) and HDL particle (HDL-P) subclasses with risk of coronary heart disease (CHD) stratified by diabetes.

Methods

We included 393,516 participants (20,691 diabetics and 372,825 nondiabetics) from the UK Biobank. Restricted cubic splines cooperated with Cox model were used to estimate associations of HDL with CHD.

Results

During a median follow-up of 13.0 years, 3398 (16.4 %) and 24,772 (6.6 %) incident CHD events occurred among diabetics and nondiabetics, respectively. HDL-C showed inverse associations with CHD among nondiabetics, whereas U-shaped associations among diabetics. Compared to individuals with normal HDL-C (40th - 60th percentile, 1.32–1.51 mmol/L), those in the top percentile (95th, >2.16 mmol/L) had lower CHD risks among nondiabetics (Hazard Ratio, 0.79; 95 % confidence interval, 0.73–0.86), but higher risks among diabetics (1.38, 1.02–1.88). As for HDL-P, there were inverted U-shaped associations of very large HDL-P and linearly negative associations of large HDL-P with CHD among nondiabetics; however, linearly positive associations of very large HDL-P and null associations of large HDL were observed among diabetics. L-shaped associations of medium and small HDL-P were found both in diabetics and nondiabetics.

Conclusions

Very high HDL-C levels were associated with lower CHD risks in nondiabetics, but higher risks in diabetics. Smaller HDL-P was negatively, whereas very large HDL-P was positively associated with CHD risk in diabetics. These data advance our knowledge about the interactions between HDL and diabetes.

背景和目的高密度脂蛋白（HDL）可能会在糖尿病患者中失去保护动脉粥样硬化的功能。我们试图研究按糖尿病分层的高密度脂蛋白胆固醇（HDL-C）和高密度脂蛋白颗粒（HDL-P）亚类与冠心病（CHD）风险的关系。结果在中位随访 13.0 年期间，糖尿病患者和非糖尿病患者分别发生了 3398 例（16.4%）和 24772 例（6.6%）冠心病事件。非糖尿病患者的高密度脂蛋白胆固醇与冠心病呈反向关系，而糖尿病患者的高密度脂蛋白胆固醇与冠心病呈 U 型关系。与高密度脂蛋白胆固醇正常者（第40-60百分位数，1.32-1.51毫摩尔/升）相比，那些处于最高百分位数（第95百分位数，>2.16毫摩尔/升）的非糖尿病患者发生冠心病的风险较低（危险比，0.79；95%置信区间，0.73-0.86），但糖尿病患者发生冠心病的风险较高（1.38，1.02-1.88）。至于高密度脂蛋白-P，在非糖尿病患者中，超大型高密度脂蛋白-P 与冠心病呈倒 U 型关系，大型高密度脂蛋白-P 与冠心病呈线性负相关；但在糖尿病患者中，超大型高密度脂蛋白-P 与冠心病呈线性正相关，大型高密度脂蛋白与冠心病呈负相关。结论超高 HDL-C 水平与非糖尿病患者较低的冠心病风险相关，但与糖尿病患者较高的冠心病风险相关。较小的 HDL-P 与糖尿病患者的冠心病风险呈负相关，而很大的 HDL-P 与冠心病风险呈正相关。这些数据增进了我们对高密度脂蛋白与糖尿病之间相互作用的了解。

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引用次数: 0

Cardiovascular risk in ANCA-associated vasculitis: Monocyte phenotyping reveals distinctive signatures between serological subsets ANCA相关性血管炎的心血管风险：单核细胞表型揭示血清学亚群之间的独特特征

IF 4.9 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2024-08-10 DOI: 10.1016/j.atherosclerosis.2024.118559

Yosta Vegting , Katie ML. Hanford , Aldo Jongejan , Gayle RS. Gajadin , Miranda Versloot , Nelly D. van der Bom-Baylon , Tamara Dekker , E. Lars Penne , Joost W. van der Heijden , Eline Houben , Frederike J. Bemelman , Annette E. Neele , Perry D. Moerland , Liffert Vogt , Jeffrey Kroon , Marc L. Hilhorst

Background and aims

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) is associated with an increased cardiovascular risk, particularly the myeloperoxidase AAV serotype (MPO-AAV). Distinct alterations in monocyte phenotypes may cause accelerated atherosclerotic disease in AAV.

Methods

A cohort including 43 AAV patients and 19 healthy controls was included for downstream analyses. Extensive phenotyping of monocytes and monocyte-derived macrophages was performed using bulk RNA-sequencing and flow cytometry. An in vitro transendothelial migration assay reflecting intrinsic adhesive and migratory capacities of monocytes was employed. Subsequent sub-analyses were performed to investigate differences between serological subtypes.

Results

Monocyte subset analysis showed increased classical monocytes during active disease, whereas non-classical monocytes were decreased compared to healthy controls (HC). RNA-sequencing revealed upregulation of distinct inflammatory pathways and lipid metabolism-related markers in monocytes of active AAV patients. No differences were detected in the intrinsic monocyte adhesion and migration capacity. Compared to proteinase-3(PR3)-AAV, monocytes of MPO-AAV patients in remission expressed genes related to inflammation, coagulation, platelet-binding and interferon signalling, whereas the expression of chemokine receptors indicative of acute inflammation and monocyte extravasation (i.e., CCR2 and CCR5) was increased in monocytes of PR3-AAV patients. During active disease, PR3-AAV was linked with elevated serum CRP and increased platelet counts compared to MPO-AAV.

Conclusions

These findings highlight changes in monocyte subset composition and activation, but not in the intrinsic migration capacity of AAV monocytes. MPO-AAV monocytes are associated with sustained upregulation of inflammatory genes, whereas PR3-AAV monocytes exhibit chemokine receptor upregulation. These molecular changes may play a role in elevating cardiovascular risk as well as in the underlying pathophysiology of AAV.

背景和目的抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）与心血管风险增加有关，尤其是髓过氧化物酶AAV血清型（MPO-AAV）。单核细胞表型的不同改变可能会导致 AAV 患者动脉粥样硬化疾病的加速。使用大量 RNA 序列测定和流式细胞仪对单核细胞和单核细胞衍生巨噬细胞进行了广泛的表型分析。采用了反映单核细胞内在粘附和迁移能力的体外跨内皮迁移试验。结果单核细胞亚群分析表明，与健康对照组（HC）相比，活动性疾病期间经典单核细胞增多，而非经典单核细胞减少。RNA 序列分析显示，活动期 AAV 患者单核细胞中不同炎症通路和脂质代谢相关标记物的上调。在单核细胞固有的粘附和迁移能力方面未发现差异。与蛋白酶-3（PR3）-AAV相比，处于缓解期的MPO-AAV患者的单核细胞表达了与炎症、凝血、血小板结合和干扰素信号有关的基因，而PR3-AAV患者的单核细胞表达了表明急性炎症和单核细胞外渗的趋化因子受体（即CCR2和CCR5）。在疾病活动期，与 MPO-AAV 相比，PR3-AAV 与血清 CRP 升高和血小板计数增加有关。MPO-AAV 单核细胞与炎症基因的持续上调有关，而 PR3-AAV 单核细胞则表现出趋化因子受体的上调。这些分子变化可能在增加心血管风险以及 AAV 的潜在病理生理学中发挥作用。

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引用次数: 0

Low-density lipoprotein-cholesterol and subclinical coronary atherosclerosis in a middle-aged asymptomatic U.S. population: The Miami Heart Study at Baptist Health South Florida 美国中年无症状人群中的低密度脂蛋白胆固醇和亚临床冠状动脉粥样硬化：南佛罗里达浸信会健康中心的迈阿密心脏研究

IF 4.9 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis

Pub Date : 2024-08-08 DOI: 10.1016/j.atherosclerosis.2024.118551

Kobina Hagan , Reed Mszar , Miguel Cainzos-Achirica , Michael J. Blaha , Michael D. Shapiro , Lara Arias , Anshul Saxena , Ricardo Cury , Matthew J. Budoff , Theodore Feldman , Jonathan Fialkow , Sadeer Al-Kindi , Khurram Nasir

Background and aims

We aimed to investigate the interplay between low-density lipoprotein-cholesterol (LDL-C) and coronary plaque in asymptomatic cohorts undergoing coronary tomography angiography (CCTA) assessment in the United States.

Methods

A cross-sectional analysis of baseline data from 1808 statin-naïve participants in the Miami Heart Study was conducted. We assessed CCTA-detected atherosclerosis (any plaque, noncalcified plaque, maximal stenosis ≥50%, high-risk plaque) across LDL-C levels, coronary artery calcium (CAC) scores (0, 1–99, ≥100), and 10-year cardiovascular risk categories.

Results

Atherosclerosis presence varied across LDL-C levels: 40% of those with LDL-C ≥190 mg/dL had no coronary plaque, while 33% with LDL-C <70 mg/dL had plaque (22.4% with noncalcified plaque). Among those with CAC 0, plaque prevalence ranged from 13.2% (LDL-C <70 mg/dL) to 28.2% (LDL-C ≥190 mg/dL), noncalcified plaque from 13.2% to 25.6%, stenosis ≥50% from 0 to 2.6%, and high-risk plaque from 0 to 5.1%. Conversely, with CAC ≥100, all had coronary plaque, with noncalcified plaque prevalence ranging from 25.0% (LDL-C <70 mg/dL) to 83.3% (LDL-C ≥190 mg/dL), stenosis ≥50% from 25.0% to 50.0%, and high-risk plaque from 0 to 66.7%. Among low-risk participants, 76.7% had CAC 0, yet 31.5% had any plaque and 18.3% had noncalcified plaque. Positive trends between LDL-C and any plaque (17.9%–45.2%) or noncalcified plaque (12.8%–23.8%) were observed in the low-risk group, but no clear trends were seen in higher-risk groups.

Conclusions

Heterogeneity exists in subclinical atherosclerosis across LDL-C, CAC, and estimated cardiovascular risk levels. The value of CCTA in risk-stratifying asymptomatic adults should be further explored.

背景和目的我们旨在研究在美国接受冠状动脉断层扫描（CCTA）评估的无症状人群中，低密度脂蛋白胆固醇（LDL-C）和冠状动脉斑块之间的相互作用。方法我们对迈阿密心脏研究（Miami Heart Study）中 1808 名他汀类药物无效参与者的基线数据进行了横断面分析。我们根据低密度脂蛋白胆固醇（LDL-C）水平、冠状动脉钙化（CAC）评分（0、1-99、≥100）和 10 年心血管风险类别对 CCTA 检测到的动脉粥样硬化（任何斑块、非钙化斑块、最大狭窄≥50%、高危斑块）进行了评估。结果动脉粥样硬化的存在因 LDL-C 水平而异：LDL-C ≥190 mg/dL 的人中有 40% 没有冠状动脉斑块，而 LDL-C <70 mg/dL 的人中有 33% 有斑块（22.4% 有非钙化斑块）。在 CAC 为 0 的人群中，斑块发生率从 13.2% （LDL-C <70 mg/dL）到 28.2%（LDL-C ≥190 mg/dL）不等，非钙化斑块发生率从 13.2% 到 25.6%，狭窄≥50% 的发生率从 0 到 2.6%，高危斑块发生率从 0 到 5.1%。相反，如果 CAC ≥100，则所有人都有冠状动脉斑块，非钙化斑块的发生率从 25.0% （LDL-C <70 mg/dL）到 83.3%（LDL-C ≥190 mg/dL）不等，狭窄≥50% 的发生率从 25.0% 到 50.0%，高风险斑块的发生率从 0 到 66.7%。在低风险参与者中，76.7%的人有CAC 0，但31.5%的人有任何斑块，18.3%的人有非钙化斑块。在低风险组中观察到 LDL-C 与任何斑块（17.9%-45.2%）或非钙化斑块（12.8%-23.8%）之间的正趋势，但在高风险组中未见明显趋势。CCTA在无症状成人风险分层中的价值有待进一步探讨。

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