缺氧相关性肺动脉高压新靶标:LOX-1

张卫芳; 葛晓月; 祝田田; 熊爱珍; 胡长平

doi:10.13201/j.issn.1001-1439.2018.05.022

缺氧相关性肺动脉高压新靶标:LOX-1

- 1 南昌大学第二附属医院药学部(南昌, 330006);
- 2 中南大学药学院药理学系;
- 3 新乡医学院药学院
基金项目:
国家自然科学基金 (No:81460010, 81473209)

江西省科技厅青年科学基金 (No:20171BAB215002)

中国博士后科学基金 (No:2017M622107)

江西省博士后科研择优资助项目 (No:2016KY51)

详细信息

通讯作者: 胡长平,E-mail:huchangping@csu.edu.cn

中图分类号: R544.1

收稿日期: 2017-12-30

修回日期: 2018-03-19

New target for hypoxia-induced pulmonary hypertension:LOX-1

- 1 Department of Pharmacy, bDepartment of Cardiology, the Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China;
- 2 Department of Pharmacology, School of Pharmaceutical Science, Central South University;
- 3 School of Pharmaceutical Science, Xin Xiang Medical University

More Information

Corresponding author: HU Changping, E-mail: huchangping@csu.edu.cn

Received Date: 30 December 2017

Revised Date: 19 March 2018

摘要

摘要: 肺动脉高压 (pulmonary hypertension, PH) 是一种以肺小动脉进行性重构为特征的恶性心血管疾病。其主要病因为肺小动脉原发病变所导致的肺动脉阻力增加, 最终可导致患者因右心衰竭死亡。PH的病因涉及环境与遗传因素, 其发病机制尚未完全阐明, 目前仍缺乏有效治疗手段。新近发现植物凝集素样氧化性低密度脂蛋白受体-1 (lectin-like oxidized low density lipoprotein recepter-1, LOX-1) 在低氧PH的肺血管及右心重构中均有重要作用, 有望成为治疗低氧PH新的分子靶点。本文现将LOX-1在低氧PH中的作用作一综述。
- 肺动脉高压 /
- 低氧 /
- 植物凝集素样氧化性低密度脂蛋白受体-1 /
- 血管重构 /
- 右心重构 /
- 靶向治疗
Abstract: Pulmonary hypertension (PH) is a chronic progressive vascular remodeling disease.The consequence is an increased pulmonary vascular resistance resulting in PH and progressive right heart failure and death.Although environmental, and genetic factors have been shown to affect PH, the pathogenesis are not completely clarified and an effective therapy for PH is still lacking.Recently, both foreign scholars and our group found lectinlike oxidized low density lipoprotein recepter-1 (LOX-1) has an important role in vascular remodeling and right ventricular hypertrophy in hypoxia-induced PH, which will be the potential therapeutic strategies for PH.This review will focus on the role of LOX-1 in the genesis and development of hypoxia-induced PH.
- pulmonary hypertension /
- hypoxia /
- lectin-like oxidized low density lipoprotein recepter-1 /
- vascular remodeling /
- right ventricular hypertrophy /
- targeted therapy

HTML全文

参考文献(28)

[1]	Rosenkranz S.Pulmonary hypertension 2015:current definitions,terminology,and novel treatment options[J].Clin Res Cardiol,2015,104(3):197-207.
[2]	Rich S,Dantzker DR,Ayres SM,et al.Primary pulmonary hypertension.A national prospective study[J].Ann Intern Med,1987,107(2):216-223.
[3]	D'alonzo GE,Barst RJ,Ayres SM,et al.Survival in patients with primary pulmonary hypertension.Results from a national prospective registry[J].Ann Intern Med,1991,115(5):343-349.
[4]	朱晨曦,杨京华,王增智,等.贝前列素钠与西地那非治疗肺动脉高压的疗效及安全性研究[J].临床心血管病杂志,2015,31(6):639-644.
[5]	Hoeper MM,Huscher D,Ghofrani HA,et al.Elderly patients diagnosed with idiopathic pulmonary arterial hypertension:results from the COMPERA registry[J].Int J Cardiol,2013,168(2):871-880.
[6]	何建国,杨涛.肺动脉高压治疗新视野[J].中国循环杂志,2014,29(10):761-763.
[7]	Montani D,Chaumais MC,Guignabert C,et al.Targeted therapies in pulmonary arterial hypertension[J].Pharmacol Ther,2014,141(2):172-191.
[8]	Nagase M,Hirose S,Sawamura T,et al.Enhanced expression of endothelial oxidized low-density lipoprotein receptor (LOX-1) in hypertensive rats[J].Biochem Biophys Res Commun,1997,237(3):496-498.
[9]	Ogura S,Kakino A,Sato Y,et al.LOX-1:the multifunctional receptor underlying cardiovascular dysfunction[J].Circ J,2009,73(11):1993-1999.
[10]	Sawamura T,Kume N,Aoyama T,et al.An endothelial receptor for oxidized low-density lipoprotein[J].Nature,1997,386(6620):73-77.
[11]	Yoshida H,Kondratenko N,Green S,et al.Identification of the lectin-like receptor for oxidized low-density lipoprotein in human macrophages and its potential role as a scavenger receptor[J].Biochem J,1998,334(Pt 1):9-13.
[12]	Chistiakov DA,Orekhov AN,Bobryshev YV.LOX-1-Mediated Effects on Vascular Cells in Atherosclerosis[J].Cell Physiol Biochem,2016,38(5):1851-1859.
[13]	Hu C,Mehta J.Biology of LOX-1 in relation to atherogenesis[J].Future lipidol,2008,3(6):689-696.
[14]	Yan M,Mehta JL,Zhang W,et al.LOX-1,oxidative stress and inflammation:a novel mechanism for diabetic cardiovascular complications[J].Cardiovasc Drugs Ther,2011,25(5):451-459.
[15]	余静,刘先哲.植物血凝素样氧化低密度脂蛋白受体-1与动脉粥样硬化[J].临床心血管病杂志,2008,24(9):643-646.
[16]	Wynants M,Quarck R,Ronisz A,et al.Effects of C-reactive protein on human pulmonary vascular cells in chronic thromboembolic pulmonary hypertension[J].Eur Respir J,2012,40(4):886-894.
[17]	Ogura S,Shimosawa T,Mu S,et al.Oxidative stress augments pulmonary hypertension in chronically hypoxic mice overexpressing the oxidized LDL receptor[J].Am J Physiol Heart Circ Physiol,2013,305(2):H155-162.
[18]	Johnson SM,Grosshans H,SHINGARA J,et al.RAS is regulated by the let-7 microRNA family[J].Cell,2005,120(5):635-647.
[19]	Dangi-garimella S,Yun J,Eves EM,et al.Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7[J].EMBO J,2009,28(4):347-358.
[20]	Zhang WF,Xiong YW,Zhu TT,et al.MicroRNA let-7g inhibited hypoxia-induced proliferation of PASMCs via G0/G1 cell cycle arrest by targeting c-myc[J].Life Sci,2017,170:9-15.
[21]	Zhang WF,Zhu TT,Xiong YW,et al.Negative feedback regulation between microRNA let-7g and LOX-1 mediated hypoxia-induced PASMCs proliferation[J].Biochem Biophys Res Commun,2017,488(4):655-663.
[22]	Wang DZ,Olson EN.Control of smooth muscle development by the myocardin family of transcriptional coactivators[J].Curr Opin Genet Dev,2004,14(5):558-566.
[23]	Zhang W,Zhu T,Wu W,et al.LOX-1 mediated phenotypic switching of pulmonary arterial smooth muscle cells contributes to hypoxic pulmonary hypertension[J].Eur J Pharmacol,2017,818:84-95.
[24]	Zhu TT,Zhang WF,Luo P,et al.LOX-1 promotes right ventricular hypertrophy in hypoxia-exposed rats[J].Life Sci,2017,174:35-42.
[25]	林清飞,王华军,林静,等.虾青素对糖尿病大鼠血管内皮功能的保护作用及机制[J].中华高血压杂志,2015,23(6):530-536.
[26]	Zhang MZ,Qian DH,Xu JC,et al.Statins may be beneficial for patients with pulmonary hypertension secondary to lung diseases[J].J Thorac Dis,2017,9(8):2437-2446.
[27]	Chen M,Narumiya S,Masaki T,et al.Conserved C-terminal residues within the lectin-like domain of LOX-1 are essential for oxidized low-density-lipoprotein binding[J].Biochem J,2001,355(Pt 2):289-296.
[28]	陈霞,肖煦.载LOX-1-siRNA靶向超声微泡的制备及其对大鼠动脉粥样硬化斑块的生物学作用[J].第三军医大学学报,2017,39(24):2359-2365.