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Clinical Service Quality and Unmet Needs in Homozygous Familial Hypercholesterolaemia Patients: Insights from UK Tertiary Centres 同型家族性高胆固醇血症患者的临床服务质量和未满足的需求：来自英国三级医疗中心的启示
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE
Atherosclerosis plus
Pub Date : 2024-09-01 DOI: 10.1016/j.athplu.2024.08.022
Heleen A. Hussein , Haya Haso , Bilal Bashir , Raabya Pasha , Anoushka Kamath , Maryam Ferdousi , Handrean Soran , Mariamma Baptist , Kirsty Nicholson
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引用次数: 0
Total Circulating PCSK9 Positively Correlates with Age and Free Circulating PCSK9 Positively Correlated with Body Mass Index in Healthy Volunteers 健康志愿者的总循环 PCSK9 与年龄呈正相关，游离循环 PCSK9 与体重指数呈正相关
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE
Atherosclerosis plus
Pub Date : 2024-09-01 DOI: 10.1016/j.athplu.2024.08.006
Anoushka Kamath , Maryam Ferdousi , Bilal Bashir , Raabya Pasha , Handrean Soran
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引用次数: 0
The pro-atherogenic enzyme PAPP-A is active in eluates from human carotid and femoral atherosclerotic plaques 促动脉粥样硬化酶 PAPP-A 在人体颈动脉和股动脉粥样硬化斑块的洗脱液中具有活性
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE
Atherosclerosis plus
Pub Date : 2024-09-01 DOI: 10.1016/j.athplu.2024.09.001
Mette Faurholdt Gude , Rikke Hjortebjerg , Mette Bjerre , Anne Kathrine Nissen Pedersen , Claus Oxvig , Lars Melholt Rasmussen , Jan Frystyk , Lasse Steffensen

Background

Pregnancy-associated plasma protein-A (PAPP-A) regulates bioavailability of insulin-like growth factor 1 (IGF1) in various tissues by proteolytic cleavage of a subset of IGF-binding proteins (IGFBPs). Pre-clinical studies have established a role of PAPP-A in atherosclerosis and proposed that targeting the proteolytic activity of PAPP-A has therapeutic value.

This study aimed to investigate whether human atherosclerotic plaques contain proteolytically active PAPP-A, a prerequisite for further considering PAPP-A as a therapeutic target in patients.

Methods

We obtained carotid (n = 9) and femoral (n = 11) atherosclerotic plaques from patients undergoing vascular surgery and incubated freshly harvested plaque tissue in culture media for 24 h. Subsequently, conditioned media were assayed for PAPP-A, STC2, IGFBP4, and IGF1 using immunoassays. Enzymatic activity of PAPP-A was assessed by its ability to process recombinant IGFBP4-IGF1 complexes - a specific substrate of PAPP-A - by Western blotting.

Results

PAPP-A and STC2 were detectable in conditioned media from both carotid and femoral plaques, with higher STC2 concentrations in eluates from carotid plaque incubations (p = 0.02). IGFBP4 and IGF1 were undetectable. Conditioned media from all 20 plaques exhibited PAPP-A proteolytic activity. However, no correlation between PAPP-A concentration and its proteolytic activity was observed, whereas the PAPP-A: STC2 molar ratio correlated with PAPP-A activity (R2 = 0.25, p = 0.03).

Conclusion

This study provides evidence for the presence of enzymatically active PAPP-A in atherosclerotic plaques and underscores the need for further investigating potential beneficial effects associated with targeting PAPP-A in atherosclerotic cardiovascular disease.

背景妊娠相关血浆蛋白-A（PAPP-A）通过蛋白水解IGF结合蛋白（IGFBPs）子集，调节胰岛素样生长因子1（IGF1）在各种组织中的生物利用率。临床前研究已经确定了 PAPP-A 在动脉粥样硬化中的作用，并提出针对 PAPP-A 的蛋白水解活性具有治疗价值。本研究旨在调查人类动脉粥样硬化斑块是否含有蛋白水解活性 PAPP-A，这是进一步考虑将 PAPP-A 作为患者治疗靶点的前提条件。方法我们从接受血管手术的患者身上获取了颈动脉（n = 9）和股动脉（n = 11）动脉粥样硬化斑块，并将新鲜获取的斑块组织在培养基中培养 24 小时，然后用免疫测定法测定条件培养基中的 PAPP-A、STC2、IGFBP4 和 IGF1。结果在颈动脉斑块和股动脉斑块的条件培养基中都能检测到 PAPP-A 和 STC2，其中颈动脉斑块培养液中的 STC2 浓度更高（p = 0.02）。IGFBP4和IGF1检测不到。所有 20 个斑块的条件培养基都显示出 PAPP-A 蛋白溶解活性。结论这项研究为动脉粥样硬化斑块中存在具有酶活性的 PAPP-A 提供了证据，并强调有必要进一步研究针对动脉粥样硬化心血管疾病的 PAPP-A 的潜在有益作用。
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引用次数: 0
A New Diagnosis of Familial Chylomicronaemia Syndrome in a 15-Year-Old Male: From Lab to Clinic 一名 15 岁男性的家族性乳糜微粒血症综合征新诊断：从实验室到临床
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE
Atherosclerosis plus
Pub Date : 2024-09-01 DOI: 10.1016/j.athplu.2024.08.004
S. Elgerray ∗ , A. Bruce , C. Saddington , L. Kayali , K. Smith , H. Divyateja
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引用次数: 0
Target gene selection and design of precise base editing therapies for atherosclerotic cardiovascular disease 针对动脉粥样硬化性心血管疾病的靶基因选择和精确碱基编辑疗法设计
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE
Atherosclerosis plus
Pub Date : 2024-09-01 DOI: 10.1016/j.athplu.2024.08.005
F.T. Fiedorek ∗ , S. Vafai , A.V. Khera , T. Lister , S. Kathiresan , A.M. Bellinger
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引用次数: 0
Ketogenic diet and extreme hypercholesterolaemia: A case of polygenic hypercholesteroalemia 生酮饮食与极端高胆固醇血症：一个多基因高胆固醇血症病例
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE
Atherosclerosis plus
Pub Date : 2024-09-01 DOI: 10.1016/j.athplu.2024.08.007
T. Mazaheri , A. David , B. Jones , J.Cegla
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引用次数: 0
Efficacy and safety of statins, ezetimibe and statins-ezetimibe therapies for children and adolescents with heterozygous familial hypercholesterolaemia: Systematic review, pairwise and network meta-analyses of randomised controlled trials 他汀类药物、依折麦布和他汀类药物-依折麦布疗法对杂合性家族性高胆固醇血症儿童和青少年的疗效和安全性：随机对照试验的系统回顾、配对分析和网络荟萃分析
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE
Atherosclerosis plus
Pub Date : 2024-09-01 DOI: 10.1016/j.athplu.2024.08.017
A. Llewellyn , M. Simmonds , D. Marshall , M. Harden , B. Woods , S.E. Humphries , U. Ramaswami , L. Priestley-Barnham , M. Fisher , L. Tata , N. Qureshi.
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引用次数: 0
Hypertriglyceridaemia and Cardiovascular Autonomic Function in Patients Without Diabetes Mellitus 高甘油三酯血症与无糖尿病患者的心血管自主神经功能
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE
Atherosclerosis plus
Pub Date : 2024-09-01 DOI: 10.1016/j.athplu.2024.08.021
Bilal Bashir , Maryam Ferdousi , Raabya Pasha , Anoushka Kamath , Handrean Soran
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引用次数: 0
The long-term, real-world effectiveness and safety of lomitapide in homozygous familial hypercholesterolaemia (HoFH): Nine-year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER) 洛米他滨对同型家族性高胆固醇血症（HoFH）的长期实际有效性和安全性：洛美他匹观察性全球评估登记处（LOWER）的九年数据
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE
Atherosclerosis plus
Pub Date : 2024-09-01 DOI: 10.1016/j.athplu.2024.08.014
Dirk Blom , Jaimini Cegla ∗ , James Underberg , Christopher P. Cannon , Dominique Larrey , Lukas Makris , Sallyann O’Brien
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引用次数: 0
Statin Treatment in Type 1 Diabetes is Not Associated with Diabetic Peripheral Neuropathy 1 型糖尿病患者接受他汀类药物治疗与糖尿病周围神经病变无关
IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE
Atherosclerosis plus
Pub Date : 2024-09-01 DOI: 10.1016/j.athplu.2024.08.009
Raabya Pasha , Zara Linn , Alise Kalteniece , Bilal Bashir , Anoushka Kamath , Eirene Kolakaluri , Mariamma Baptist , Shazli Azmi , Maryam Ferdousi , Rayaz Malik , Handrean Soran
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引用次数: 0
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