[1]朱鹤宸 朱舒舒 龙明智.脂蛋白a与血栓性疾病的研究进展[J].心血管病学进展,2025,(6):503.[doi:10.16806/j.cnki.issn.1004-3934.2025.06.006]
　ZHU Hechen,ZHU Shushu,LONG Mingzhi.Advances in the Study of Lipoprotein (a) and Thrombophilia[J].Advances in Cardiovascular Diseases,2025,(6):503.[doi:10.16806/j.cnki.issn.1004-3934.2025.06.006]
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脂蛋白a与血栓性疾病的研究进展()

《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2025年6期
页码:
503
栏目:
综述
出版日期:
2025-06-25

文章信息/Info

Title:
Advances in the Study of Lipoprotein (a) and Thrombophilia
作者:
朱鹤宸1 朱舒舒2 龙明智2
(南京医科大学附属第二医院心内科,江苏 南京 210011)
Author(s):
ZHU Hechen1; ZHU Shushu2; LONG Mingzhi2
?Department of Cardiology,The Second Affiliated Hospital of Nanjing Medical University,Nanjing 210011,Jiangsu,China)
关键词:
脂蛋白a; 纤维蛋白溶解系统; 凝血系统; 血栓; 血小板; 支架内再狭窄; 主动脉瓣狭窄
Keywords:
Lipoprotein(a); Fibrinolysis system; Coagulation system; Thrombus; Platelet; In-stent restenosis; Aortic stenosis
DOI:
10.16806/j.cnki.issn.1004-3934.2025.06.006
摘要:
脂蛋白a [Lp(a)]由载脂蛋白a、载脂蛋白B和氧化磷脂构成，经多种途径推动血小板聚集与血栓形成。高Lp(a)水平人群早年患急性冠脉综合征风险增加，主动脉瓣钙化以及支架内再狭窄风险亦显著上升。当前，反义寡核苷酸pelacarsen和干扰小RNA olpasiran虽为高Lp(a)血症患者带来曙光，但Lp(a)降低能否减少血栓性疾病发生仍未可知，现综述Lp(a)的结构形成及其与纤维蛋白溶解系统和凝血系统关系，以探讨Lp(a)对血栓性疾病的作用，为后续研究提供理论基础与思路方向。
Abstract:
Lipoprotein(a)[Lp(a)],composed of apolipoprotein(a),apolipoprotein B,and oxidized phospholipids,promotes platelet aggregation and thrombosis through multiple pathways. Individuals with elevated Lp(a) levels face an increased risk of early-onset acute coronary syndrome,aortic valve calcification,and in-stent restenosis. While therapeutic approaches such as the antisense oligonucleotide pelacarsen and the small interfering RNA olpasiran offer hope for patients with hyperlipoproteinemia(a),it remains uncertain whether reducing Lp(a) levels can effectively lower the incidence of thrombotic diseases. This review will examine the structural formation of Lp(a) and its interactions with the fibrinolytic and coagulation systems to explore its role in thrombotic diseases,providing a theoretical foundation and guidance for future research

参考文献/References:

[1]Coassin S,Chemello K,Khantalin I,et al. Genome-Wide Characterization of a Highly Penetrant Form of Hyperlipoprotein(a)emia Associated With Genetically Elevated Cardiovascular Risk[J]. Circ Genom Precis Med,2022,15(2):e003489.
[2]Lacaze P,Bakshi A,Riaz M,et al. Aspirin for primary prevention of cardiovascular events in relation to lipoprotein(a) genotypes[J]. J Am Coll Cardiol,2022,80(14):1287-1298.
[3]Wang H,Hong CE,Lewis JP,et al. Effect of two lipoprotein (a)-associated genetic variants on plasminogen levels and fibrinolysis[J]. G3 (Bethesda),2016,6(11):3525-3532.
[4]Zhang Z,Rodriguez M,Zheng Z. Clot or not? Reviewing the reciprocal regulation between lipids and blood clotting[J]. Arterioscler Thromb Vasc Biol,2024,44(3):533-544.
[5]Mayyas F,Bani Omar E. Plasma lipoprotein (a) and tissue plasminogen activator are associated with increased risk of atherosclerotic cardiovascular disease[J]. Heliyon,2022,8(7):e09836.
[6]Ugov?ek S,Rehberger Likozar A,Levstek T,et al. Haplotype of the lipoprotein(a) gene variants rs10455872 and rs3798220 is associated with parameters of coagulation,fibrinolysis,and inflammation in patients after myocardial infarction and highly elevated lipoprotein(a) values[J]. Int J Mol Sci,2024,25(2):736.
[7]Dai W,Zhang H,Lund H,et al. Intracellular tPA–PAI-1 interaction determines VLDL assembly in hepatocytes[J]. Science,2023,381(6661):eadh5207.
[8]Boffa MB. Beyond fibrinolysis:the confounding role of Lp(a) in thrombosis[J]. Atherosclerosis,2022,349:72-81.
[9]Kille A,Nüehrenberg T,Franke K,et al. Association of lipoprotein(a) with intrinsic and on-clopidogrel platelet reactivity[J]. J Thromb Thrombolysis,2022,53(1):1-9.
[10]Ugov?ek S,?ebe?tjen M. Lipoprotein(a)—The crossroads of atherosclerosis,atherothrombosis and inflammation[J]. Biomolecules,2021,12(1):26.
[11]Madsen CM,Kamstrup PR,Langsted A,et al. Lipoprotein(a)—Lowering by 50 mg/dL (105 nmol/L) may be needed to reduce cardiovascular disease 20% in secondary prevention:a population-based study[J]. Arterioscler Thromb Vasc Biol,2020,40(1):255-266.
[12]Langsted A,Kamstrup PR,Nordestgaard BG. Lipoprotein(a):fasting and nonfasting levels,inflammation,and cardiovascular risk[J]. Atherosclerosis,2014,234(1):95-101.
[13]Zhang Y,Jin JL,Cao YX,et al. Prognostic utility of lipoprotein(a) combined with fibrinogen in patients with stable coronary artery disease:a prospective,large cohort study[J]. J Transl Med,2020,18(1):373.
[14]Loewenstein I,Lichtenstein D,Goldiner I,et al. Lipoprotein(a) levels in severe aortic?stenosis referred for transcatheter aortic valve implantation compared to controls[J]. JACC Adv,2024,3(10):101264.
[15]Bhatia HS,Ma GS,Taleb A,et al. Trends in testing and prevalence of elevated Lp(a) among patients with aortic valve stenosis[J]. Atherosclerosis,2022,349:144-150.
[16]Sticchi E,Giusti B,Cordisco A,et al. Role of lipoprotein (a) and LPA KⅣ2 repeat polymorphism in bicuspid aortic valve stenosis and calcification:a proof of concept study[J]. Intern Emerg Med,2019,14(1):45-50.
[17]Santangelo G,Faggiano A,Bernardi N,et al. Lipoprotein(a) and aortic valve stenosis:a casual or causal association?[J]. Nutr Metab Cardiovasc Dis,2022,32(2):309-317.
[18]Obisesan OH,Kou M,Wang FM,et al. Lipoprotein(a) and subclinical vascular and valvular calcification on cardiac computed tomography:the atherosclerosis risk in communities study[J]. J Am Heart Assoc,2022,11(11):e024870.
[19]Zheng KH,Arsenault BJ,Kaiser Y,et al. ApoB/ApoA-Ⅰ Ratio and Lp(a) associations with aortic valve stenosis incidence:insights from the EPIC-Norfolk prospective population study[J]. J Am Heart Assoc,2019,8(16):e013020.
[20]Bhatia HS,Hurst S,Desai P,et al. Lipoprotein(a) testing trends in a large academic health system in the United States[J]. J Am Heart Assoc,2023,12(18):e031255.
[21]Wodaje T,Littmann K,H?bel H,et al. Plasma Lipoprotein(a) measured in routine clinical care and the association with incident calcified aortic valve stenosis during a 14-year observational period[J]. Atherosclerosis,2022,349:175-182.
[22]Kamstrup PR,Tybj?rg-Hansen A,Nordestgaard BG. Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population[J]. J Am Coll Cardiol,2014,63(5):470-477.
[23]Kaiser Y,van der Toorn JE,Singh SS,et al. Lipoprotein(a) is associated with the onset but not the progression of aortic valve calcification[J]. Eur Heart J,2022,43(39):3960-3967.
[24]de Boer LM,Wiegman A,van Gemert RLA,et al. The association between lipoprotein(a) levels and ischemic stroke in children:a case-control study[J]. Pediatr Blood Cancer,2024,71(10):e31236.
[25]deVeber GA,Kirton A,Booth FA,et al. Epidemiology and outcomes of arterial ischemic stroke in children:the Canadian Pediatric Ischemic Stroke Registry[J]. Pediatr Neurol,2017,69:58-70.
[26]Goldenberg NA,Bernard TJ,Hillhouse J,et al. Elevated lipoprotein (a),small apolipoprotein (a),and the risk of arterial ischemic stroke in North American children[J]. Haematologica,2013,98(5):802-807.
[27]Arnold M,Schweizer J,Nakas CT,et al. Lipoprotein(a) is associated with large artery atherosclerosis stroke aetiology and stroke recurrence among patients below the age of 60 years:results from the BIOSIGNAL study[J]. Eur Heart J,2021,42(22):2186-2196.
[28]Tsimikas S. Elevated lipoprotein(a) and the risk of stroke in children,young adults,and the elderly[J]. Eur Heart J,2021,42(22):2197-2200.
[29]Gressenberger P,Posch F,Adelsmayr G,et al. Lipoprotein (a) is not associated with thrombus burden derived from CT pulmonary angiography in patients with acute pulmonary embolism[J]. Sci Rep,2024,14(1):25962.
[30]Kronenberg F,Mora S,Stroes ESG,et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis:a European Atherosclerosis Society consensus statement[J]. Eur Heart J,2022,43(39):3925-3946.
[31]Spasi? I,Ubavi? M,?umarac Z,et al. Influence of lipid metabolism disorders on venous thrombosis risk[J]. J Med Biochem,2021,40(3):245-251.
[32]Emdin CA,Khera AV,Natarajan P,et al. Phenotypic characterization of genetically?lowered human lipoprotein(a) levels[J]. J Am Coll Cardiol,2016,68(25):2761-2772.
[33]Ding WY,Protty MB,Davies IG,et al. Relationship between lipoproteins,thrombosis,and atrial fibrillation[J]. Cardiovasc Res,2022,118(3):716-731.
[34]Marston NA,Gurmu Y,Melloni GEM,et al. The effect of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition on the risk of venous thromboembolism[J]. Circulation,2020,141(20):1600-1607.
[35]Schol-Gelok S,Galema-Boers JAMH,van Gelder T,et al. No effect of PCSK9 inhibitors on D-dimer and fibrinogen levels in patients with familial hypercholesterolemia[J]. Biomed Pharmacother,2018,108:1412-1414.
[36]Karwatowska-Prokopczuk E,Li L,Yang J,et al. On-treatment platelet reactivity through the thromboxane A2 or P2Y12 platelet receptor pathways is not affected by pelacarsen[J]. J Thromb Thrombolysis,2023,56(2):226-232.

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更新日期/Last Update: 2025-07-31