• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

载脂蛋白(a)通过整合素 αVβ3 及 RhoA/ROCK 介导的机制，作为趋化抑制剂作用于人血管平滑肌细胞。

Apolipoprotein(a) acts as a chemorepellent to human vascular smooth muscle cells via integrin αVβ3 and RhoA/ROCK-mediated mechanisms.

机构信息

Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds, UK.

出版信息

Int J Biochem Cell Biol. 2013 Aug;45(8):1776-83. doi: 10.1016/j.biocel.2013.05.021. Epub 2013 May 31.

DOI:10.1016/j.biocel.2013.05.021
PMID:23726972
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3731554/
Abstract

Lipoprotein(a) (Lp(a)) is an independent risk factor for the development of cardiovascular disease. Vascular smooth muscle cell (SMC) motility and plasticity, functions that are influenced by environmental cues, are vital to adaptation and remodelling in vascular physiology and pathophysiology. Lp(a) is reportedly damaging to SMC function via unknown molecular mechanisms. Apolipoprotein(a) (apo(a)), a unique glycoprotein moiety of Lp(a), has been demonstrated as its active component. The aims of this study were to determine functional effects of recombinant apo(a) on human vascular SMC motility and explore the underlying mechanism(s). Exposure of SMC to apo(a) in migration assays induced a potent, concentration-dependent chemorepulsion that was RhoA and integrin αVβ3-dependent, but transforming growth factor β-independent. SMC manipulation through RhoA gene silencing, Rho kinase inhibition, statin pre-treatment, αVβ3 neutralising antibody and tyrosine kinase inhibition all markedly inhibited apo(a)-mediated SMC migration. Our data reveal unique and potent activities of apo(a) that may negatively influence SMC remodelling in cardiovascular disease. Circulating levels of Lp(a) are resistant to lipid-lowering strategies and hence a greater understanding of the mechanisms underlying its functional effects on SMC may provide alternative therapeutic targets.

摘要

脂蛋白(a)（Lp(a)）是心血管疾病发展的独立危险因素。血管平滑肌细胞（SMC）的运动和可塑性是受环境线索影响的功能，对血管生理学和病理生理学的适应和重塑至关重要。据报道，Lp(a) 通过未知的分子机制对 SMC 功能造成损害。载脂蛋白(a)（apo(a)）是 Lp(a) 的独特糖蛋白部分，已被证明是其活性成分。本研究旨在确定重组 apo(a) 对人血管 SMC 运动的功能影响，并探讨潜在的机制。在迁移实验中，SMC 暴露于 apo(a) 中会诱导一种强大的、浓度依赖性的趋化排斥作用，该作用依赖于 RhoA 和整合素 αVβ3，但不依赖于转化生长因子β。通过 RhoA 基因沉默、Rho 激酶抑制、他汀类药物预处理、αVβ3 中和抗体和酪氨酸激酶抑制对 SMC 进行操作，均可显著抑制 apo(a)介导的 SMC 迁移。我们的数据揭示了 apo(a) 的独特而强大的活性，可能会对心血管疾病中的 SMC 重塑产生负面影响。循环中的 Lp(a) 水平不受降脂策略的影响，因此，深入了解其对 SMC 功能的作用机制可能为提供替代治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1335/3731554/b6fef795b90a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1335/3731554/85bfa9e73b03/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1335/3731554/24b888e90d20/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1335/3731554/044f58d54e99/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1335/3731554/51403cbac2b4/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1335/3731554/307dabb16f85/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1335/3731554/9e273d45f59d/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1335/3731554/b6fef795b90a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1335/3731554/85bfa9e73b03/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1335/3731554/24b888e90d20/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1335/3731554/044f58d54e99/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1335/3731554/51403cbac2b4/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1335/3731554/307dabb16f85/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1335/3731554/9e273d45f59d/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1335/3731554/b6fef795b90a/gr6.jpg

相似文献

1
Apolipoprotein(a) acts as a chemorepellent to human vascular smooth muscle cells via integrin αVβ3 and RhoA/ROCK-mediated mechanisms.载脂蛋白(a)通过整合素 αVβ3 及 RhoA/ROCK 介导的机制，作为趋化抑制剂作用于人血管平滑肌细胞。
Int J Biochem Cell Biol. 2013 Aug;45(8):1776-83. doi: 10.1016/j.biocel.2013.05.021. Epub 2013 May 31.
2
Apolipoprotein(a) stimulates vascular endothelial cell growth and migration and signals through integrin alphaVbeta3.载脂蛋白(a)刺激血管内皮细胞生长和迁移，并通过整合素αVβ3发出信号。
Biochem J. 2009 Mar 1;418(2):325-36. doi: 10.1042/BJ20080744.
3
Rho/ROCK signal cascade mediates asymmetric dimethylarginine-induced vascular smooth muscle cells migration and phenotype change.Rho/ROCK信号级联介导不对称二甲基精氨酸诱导的血管平滑肌细胞迁移和表型改变。
Biomed Res Int. 2014;2014:683707. doi: 10.1155/2014/683707. Epub 2014 Jul 9.
4
Transforming growth factor-beta1-induced expression of smooth muscle marker genes involves activation of PKN and p38 MAPK.转化生长因子-β1诱导的平滑肌标记基因表达涉及PKN和p38丝裂原活化蛋白激酶的激活。
J Biol Chem. 2005 Sep 2;280(35):31172-81. doi: 10.1074/jbc.M504774200. Epub 2005 Jun 26.
5
Modification of PI3K- and MAPK-dependent chemotaxis in aortic vascular smooth muscle cells by protein kinase CbetaII.蛋白激酶CβII对主动脉血管平滑肌细胞中PI3K和MAPK依赖性趋化作用的调节
Circ Res. 2005 Feb 4;96(2):197-206. doi: 10.1161/01.RES.0000152966.88353.9d. Epub 2004 Dec 9.
6
The Lbc Rho guanine nucleotide exchange factor α-catulin axis functions in serotonin-induced vascular smooth muscle cell mitogenesis and RhoA/ROCK activation.Lbc Rho 鸟嘌呤核苷酸交换因子 α-微管蛋白在 5-羟色胺诱导的血管平滑肌细胞有丝分裂和 RhoA/ROCK 激活中起作用。
J Biol Chem. 2010 Oct 22;285(43):32919-32926. doi: 10.1074/jbc.M109.062513. Epub 2010 Aug 9.
7
RhoA/ROCK signaling regulates smooth muscle phenotypic modulation and vascular remodeling via the JNK pathway and vimentin cytoskeleton.RhoA/ROCK 信号通路通过 JNK 通路和波形蛋白细胞骨架调节平滑肌表型调节和血管重塑。
Pharmacol Res. 2018 Jul;133:201-212. doi: 10.1016/j.phrs.2018.05.011. Epub 2018 May 20.
8
Sphingosine 1-phosphate stimulates smooth muscle cell differentiation and proliferation by activating separate serum response factor co-factors.鞘氨醇-1-磷酸通过激活不同的血清反应因子辅助因子来刺激平滑肌细胞的分化和增殖。
J Biol Chem. 2004 Oct 8;279(41):42422-30. doi: 10.1074/jbc.M405432200. Epub 2004 Aug 3.
9
Platelet-derived growth factor-BB-induced hypertrophy of peritubular smooth muscle cells is mediated by activation of p38 MAP-kinase and of Rho-kinase.血小板衍生生长因子-BB诱导的肾小管周平滑肌细胞肥大是由p38丝裂原活化蛋白激酶和Rho激酶的激活介导的。
J Cell Physiol. 2006 Apr;207(1):123-31. doi: 10.1002/jcp.20554.
10
Simvastatin inhibits MMP-9 secretion from human saphenous vein smooth muscle cells by inhibiting the RhoA/ROCK pathway and reducing MMP-9 mRNA levels.辛伐他汀通过抑制RhoA/ROCK途径并降低MMP-9 mRNA水平，抑制人隐静脉平滑肌细胞分泌MMP-9。
FASEB J. 2005 May;19(7):804-6. doi: 10.1096/fj.04-2852fje. Epub 2005 Feb 23.

引用本文的文献

1
Secretory Profile Analysis of Human Granulosa Cell Line Following Gonadotropin Stimulation.促性腺激素刺激后人颗粒细胞系的分泌谱分析
Int J Mol Sci. 2025 Apr 25;26(9):4108. doi: 10.3390/ijms26094108.
2
Bibliometric analysis of residual cardiovascular risk: trends and frontiers.基于文献计量学的残余心血管风险分析：趋势与前沿。
J Health Popul Nutr. 2023 Nov 28;42(1):132. doi: 10.1186/s41043-023-00478-z.
3
Lipoprotein(a): Just an Innocent Bystander in Arterial Hypertension?脂蛋白(a)：仅仅是高血压的无辜旁观者吗？

本文引用的文献

1
Lipoprotein(a): Cellular Effects and Molecular Mechanisms.脂蛋白(a)：细胞效应与分子机制。
Cholesterol. 2012;2012:923289. doi: 10.1155/2012/923289. Epub 2012 Sep 6.
2
Lipoprotein(a) as a potential causal genetic risk factor of cardiovascular disease: a rationale for increased efforts to understand its pathophysiology and develop targeted therapies.脂蛋白(a)作为心血管疾病潜在的因果遗传风险因素：增加对其病理生理学理解和开发靶向治疗的努力的理由。
J Am Coll Cardiol. 2012 Aug 21;60(8):716-21. doi: 10.1016/j.jacc.2012.04.038.
3
Lipoprotein (a) and carotid atherosclerosis in young patients with stroke.
Int J Mol Sci. 2023 Aug 29;24(17):13363. doi: 10.3390/ijms241713363.
4
Lipoprotein(a): a Case for Universal Screening in Youth.脂蛋白(a)：在青年人群中进行普遍筛查的理由。
Curr Atheroscler Rep. 2023 Aug;25(8):487-493. doi: 10.1007/s11883-023-01120-3. Epub 2023 Jul 5.
5
Lipoprotein(a) in Atherosclerotic Diseases: From Pathophysiology to Diagnosis and Treatment.脂蛋白(a)在动脉粥样硬化疾病中的作用：从病理生理学到诊断与治疗。
Molecules. 2023 Jan 18;28(3):969. doi: 10.3390/molecules28030969.
6
Apolipoprotein (a)/Lipoprotein(a)-Induced Oxidative-Inflammatory 7-nAChR/p38 MAPK/IL-6/RhoA-GTP Signaling Axis and M1 Macrophage Polarization Modulate Inflammation-Associated Development of Coronary Artery Spasm.载脂蛋白（a）/脂蛋白（a）诱导的氧化炎症 7 型烟碱型乙酰胆碱受体/p38MAPK/IL-6/RhoA-GTP 信号轴和 M1 巨噬细胞极化调节炎症相关的冠状动脉痉挛发展。
Oxid Med Cell Longev. 2022 Jan 19;2022:9964689. doi: 10.1155/2022/9964689. eCollection 2022.
7
Lipoprotein (a) and Hypertension.脂蛋白(a)与高血压。
Curr Hypertens Rep. 2021 Dec 9;23(12):44. doi: 10.1007/s11906-021-01161-6.
8
Using to Develop Therapeutics for Acute Respiratory Distress Syndrome.利用[具体内容]开发急性呼吸窘迫综合征的治疗方法。 （你提供的原文“Using to Develop Therapeutics for Acute Respiratory Distress Syndrome.”中“Using”后缺少具体内容，我按照常规补充了“[具体内容]”来使译文逻辑完整，你可根据实际情况修改。）
Front Cell Dev Biol. 2021 Jul 19;9:710005. doi: 10.3389/fcell.2021.710005. eCollection 2021.
9
Garcinol Attenuates Lipoprotein(a)-Induced Oxidative Stress and Inflammatory Cytokine Production in Ventricular Cardiomyocyte through α7-Nicotinic Acetylcholine Receptor-Mediated Inhibition of the p38 MAPK and NF-κB Signaling Pathways.藤黄脂素通过α7-烟碱型乙酰胆碱受体介导的对p38丝裂原活化蛋白激酶和核因子κB信号通路的抑制作用，减轻脂蛋白(a)诱导的心室心肌细胞氧化应激和炎性细胞因子生成。
Antioxidants (Basel). 2021 Mar 16;10(3):461. doi: 10.3390/antiox10030461.
10
Recent Updates of Lipoprotein(a) and Cardiovascular Disease.脂蛋白(a)与心血管疾病的最新进展
Chonnam Med J. 2021 Jan;57(1):36-43. doi: 10.4068/cmj.2021.57.1.36. Epub 2021 Jan 25.
脂蛋白（a）与青年脑卒中患者颈动脉粥样硬化
Stroke. 2011 Dec;42(12):3616-8. doi: 10.1161/STROKEAHA.111.624684. Epub 2011 Sep 22.
4
Statins and myocardial remodelling: cell and molecular pathways.他汀类药物与心肌重构：细胞和分子途径。
Expert Rev Mol Med. 2011 Jul 1;13:e22. doi: 10.1017/S1462399411001931.
5
Genetic variants associated with Lp(a) lipoprotein level and coronary disease.与脂蛋白(a)水平和冠心病相关的遗传变异。
N Engl J Med. 2009 Dec 24;361(26):2518-28. doi: 10.1056/NEJMoa0902604.
6
Adaptive changes in autogenous vein grafts for arterial reconstruction: clinical implications.自体静脉移植物在动脉重建中的适应性变化：临床意义。
J Vasc Surg. 2010 Mar;51(3):736-46. doi: 10.1016/j.jvs.2009.07.102. Epub 2009 Oct 17.
7
Absence of Akt1 reduces vascular smooth muscle cell migration and survival and induces features of plaque vulnerability and cardiac dysfunction during atherosclerosis.Akt1的缺失会减少血管平滑肌细胞的迁移和存活，并在动脉粥样硬化过程中诱发斑块易损性和心脏功能障碍的特征。
Arterioscler Thromb Vasc Biol. 2009 Dec;29(12):2033-40. doi: 10.1161/ATVBAHA.109.196394. Epub 2009 Sep 17.
8
Apoptosis, cell proliferation and modulation of cyclin-dependent kinase inhibitor p21(cip1) in vascular remodelling during vein arterialization in the rat.大鼠静脉动脉化过程中血管重塑时的细胞凋亡、细胞增殖及细胞周期蛋白依赖性激酶抑制剂p21（cip1）的调节
Int J Exp Pathol. 2009 Jun;90(3):328-37. doi: 10.1111/j.1365-2613.2009.00648.x.
9
Apolipoprotein(a) stimulates vascular endothelial cell growth and migration and signals through integrin alphaVbeta3.载脂蛋白(a)刺激血管内皮细胞生长和迁移，并通过整合素αVβ3发出信号。
Biochem J. 2009 Mar 1;418(2):325-36. doi: 10.1042/BJ20080744.
10
Apolipoprotein(a), through its strong lysine-binding site in KIV(10'), mediates increased endothelial cell contraction and permeability via a Rho/Rho kinase/MYPT1-dependent pathway.载脂蛋白(a)通过其在KIV(10')中的强赖氨酸结合位点，经由Rho/Rho激酶/MYPT1依赖性途径介导内皮细胞收缩和通透性增加。
J Biol Chem. 2008 Nov 7;283(45):30503-12. doi: 10.1074/jbc.M802648200. Epub 2008 Sep 5.