心力衰竭的潜在治疗靶点及相关药物研发进展

杨梅; 王平; 杨晖; 何功浩

doi:10.12259/j.issn.2095-610X.S20230719

心力衰竭的潜在治疗靶点及相关药物研发进展

doi: 10.12259/j.issn.2095-610X.S20230719

杨梅¹,
王平¹,
杨晖²,
何功浩^1, ,

1.
中国人民解放军联勤保障部队第九二〇医院临床药学科，云南昆明　650032
2.
昆明医科大学生物医学工程研究院，云南昆明　650500

基金项目: 国家自然科学基金资助项目（81960664）；云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目（202101AY070001-300）

详细信息

作者简介:
杨梅（1995～），女，云南昭通人，在读硕士研究生，主要从事分子药理学工作

通讯作者:
何功浩，E-mail：gonghow@hotmail.com

中图分类号: R541.6
计量
- 文章访问数: 4224
- HTML全文浏览量: 2611
- PDF下载量: 112
- 被引次数: 0
出版历程
- 收稿日期: 2022-03-01
- 网络出版日期: 2023-07-18
- 刊出日期: 2023-07-25

Potential Therapeutic Targets and Research Progress of Related Drugs of Heart Failure

1.
Dept. of Clinical Pharmacy，920th Hospital of Joint Logistics Support Force of People’s Liberation Army，Kunming Yunan 650032
2.
Biomedical Engineering Research Center，Kunming Medical University，Kunming Yunnan 650500，China

摘要

摘要: 心力衰竭是心血管病主要死亡原因之一，随着心力衰竭患病率不断增加，探索寻找新的治疗靶点，进一步减少患者病死率，成为心力衰竭治疗的主要研究方向。主要通过对国内外发表的心力衰竭治疗靶点相关研究论文进行检索和整理，分类综述心力衰竭治疗的相关靶点，包括G蛋白偶联受体家族、Na⁺/H⁺交换体、去乙酰化酶家族、炎性细胞因子和趋化因子等，为心力衰竭治疗、新药研发提供新思路。
- 心力衰竭 /
- 靶点 /
- 药物
Abstract: Heart failure is one of the main causes of death in cardiovascular diseases. With the increasing prevalence of heart failure, it has become the main research direction to explore new therapeutic targets and further reduce the mortality of patients. This review provided a comprehensive overview of the different targets for heart failure therapy, including the G protein-coupled receptor family, Na⁺/H⁺ exchangers, deacetylase family, inflammatory cytokines and chemokines etc., by searching and collating studies related to heart failure therapeutic targets published in China and abroad. It provided new ideas for the treatment of heart failure and the development of new drugs.
- Heart failure /
- Target /
- Drug

HTML全文

参考文献(50)

[1]	Ghionzoli N,Gentile F,Del Franco A M,et al. Current and emerging drug targets in heart failure treatment[J]. Heart Fail Rev,2022,27(4):1119-1136. doi: 10.1007/s10741-021-10137-2
[2]	Castiglione V,Aimo A,Vergaro G,et al. Biomarkers for the diagnosis and management of heart failure[J]. Heart Fail Rev,2022,27(2):625-643. doi: 10.1007/s10741-021-10105-w
[3]	Bhatt K N,Butler J. Myocardial energetics and heart failure: A review of recent therapeutic trials[J]. Curr Heart Fail Rep,2018,15(3):191-197. doi: 10.1007/s11897-018-0386-8
[4]	Chen Y,He Q,Mo D C,et al. The angiotensin receptor and neprilysin inhibitor,LCZ696,in heart failure: A meta-analysis of randomized controlled trials[J]. Medicine (Baltimore),2022,101(41):e30904.
[5]	Hilger D,Masureel M,Kobilka B K. Structure and dynamics of GPCR signaling complexes[J]. Nat Struct Mol Biol,2018,25(1):4-12. doi: 10.1038/s41594-017-0011-7
[6]	Wang J,Gareri C,Rockman H A. G-protein-coupled receptors in heart disease[J]. Circ Res,2018,123(6):716-735. doi: 10.1161/CIRCRESAHA.118.311403
[7]	Rueda P,Merlin J,Chimenti S,et al. Pharmacological insights into safety and efficacy determinants for the development of adenosine receptor biased agonists in the treatment of heart failure[J]. Front Pharmacol,2021,12:628060. doi: 10.3389/fphar.2021.628060
[8]	Meibom D,Albrecht-Küpper B,Diedrichs N,et al. Neladenoson bialanate hydrochloride: A prodrug of a partial adenosineA1 receptor agonist for the chronic treatment of heart diseases[J]. Chem Med Chem,2017,12(10):728-737. doi: 10.1002/cmdc.201700151
[9]	Voors A A,Bax J J,Hernandez A F,et al. Safety and efficacy of the partial adenosine A1 receptor agonist neladenoson bialanate in patients with chronic heart failure with reduced ejection fraction: A phase IIb,randomized,double-blind,placebo-controlled trial[J]. Eur J Heart Fail,2019,21(11):1426-1433. doi: 10.1002/ejhf.1591
[10]	Neumann J,Kirchhefer U,Dhein S,et al. The roles of cardiovascular H2-histamine receptors under normal and pathophysiological conditions[J]. Front Pharmacol,2021,12:732842. doi: 10.3389/fphar.2021.732842
[11]	Saheera S,Potnuri A G,Guha A,et al. Histamine 2 receptors in cardiovascular biology: A friend for the heart[J]. Drug Discov Today,2022,27(1):234-245. doi: 10.1016/j.drudis.2021.08.008
[12]	Luo T,Chen B,Zhao Z,et al. Histamine H2 receptor activation exacerbates myocardial ischemia/reperfusion injury by disturbing mitochondrial and endothelial function[J]. Basic Res Cardiol,2013,108(3):342. doi: 10.1007/s00395-013-0342-4
[13]	Zeng Z,Shen L,Li X,et al. Disruption of histamine H2 receptor slows heart failure progression through reducing myocardial apoptosis and fibrosis[J]. Clin Sci (Lond),2014,127(7):435-48. doi: 10.1042/CS20130716
[14]	Gergs U,Kirchhefer U,Bergmann F,et al. Characterization of stressed transgenic mice overexpressing H2-histamine receptors in the heart[J]. J Pharmacol Exp Ther,2020,374(3):479-488. doi: 10.1124/jpet.120.000063
[15]	Gergs U,Büxel M L,Bresinsky M,et al. Cardiac effects of novel histamine H2 receptor agonists[J]. J Pharmacol Exp Ther,2021,379(3):223-234. doi: 10.1124/jpet.121.000822
[16]	He G,Hu J,Ma X,et al. Sympathetic histamine exerts different pre- and post-synaptic functions according to the frequencies of nerve stimulation in guinea pig vas deferens[J]. J Neurochem,2008,106(4):1710-9. doi: 10.1111/j.1471-4159.2008.05532.x
[17]	He G,Hu J,Li T,et al. Arrhythmogenic effect of sympathetic histamine in mouse hearts subjected to acute ischemia[J]. Mol Med,2012,18(1):1-9.
[18]	He G H,Cai W K,Meng J R,et al. Relation of polymorphism of the histidine decarboxylase gene to chronic heart failure in Han Chinese[J]. Am J Cardiol,2015,115(11):P1555-1562. doi: 10.1016/j.amjcard.2015.02.062
[19]	Meng R,Chen L R,Zhang M L,et al. Effectiveness and safety of histamine H2 receptor antagonists: An umbrella review of meta-analyses[J]. J Clin Pharmacol,2023,63(1):7-20. doi: 10.1002/jcph.2147
[20]	Zhang J,Cai W K,Zhang Z,et al. Cardioprotective effect of histamine H2 antagonists in congestive heart failure: A systematic review and meta-analysis[J]. Medicine (Baltimore),2018,97(15):e0409.
[21]	Huang Y H,Cai W K,Yin S J,et al. Histamine H2 receptor antagonist exposure was related to decreased all-cause mortality in critical ill patients with heart failure: A cohort study[J]. Eur J PrevCardiol,2022,29(14):1854-1865.
[22]	Sato T,Aikawa T. The role of histamine H2 receptor antagonist in heart failure: A potential game-changer?[J]. Eur J PrevCardiol,2022,29(14):1852-1853.
[23]	Liu Y,Wang Z,Li J,et al. Inhibition of 5-hydroxytryptamine receptor 2B reduced vascular restenosis and mitigated the β-arrestin2-mammalian target of rapamycin/p70S6K pathway[J]. J Am Heart Assoc,2018,7(3):e006810. doi: 10.1161/JAHA.117.006810
[24]	Cidlowski J A,Cruz-Topete D. Glucocorticoid inhibition of estrogen regulation of the serotonin receptor 2B in cardiomyocytes exacerbates cell death in hypoxia/reoxygenation injury[J]. J Am Heart Assoc,2021,10(17):e015868. doi: 10.1161/JAHA.120.015868
[25]	郝德雄,陈明,王玉兵. 5羟色胺2B受体阻滞剂对压力超负荷大鼠心功能的影响[J]. 中华高血压杂志,2016,24(9):863-868.
[26]	Janssen W,Schymura Y,Novoyatleva T,et al. 5-HT2B receptor antagonists inhibit fibrosis and protect from RV heart failure[J]. Biomed Res Int,2015,2015:438403.
[27]	Marzak H,Ayme-Dietrich E,Lawson R,et al. Old spontaneously hypertensive rats gather together typical features of human chronic left-ventricular dysfunction with preserved ejection fraction[J]. J Hypertens,2014,32(6):1307-16. doi: 10.1097/HJH.0000000000000159
[28]	Xia H,Zahra A,Jia M,et al. Na⁺/H⁺ exchanger 1,a potential therapeutic drug target for cardiac hypertrophy and heart failure[J]. Pharmaceuticals (Basel),2022,15(7):875. doi: 10.3390/ph15070875
[29]	Sjøgaard-Frich L M,Prestel A,Pedersen E S,et al. Dynamic Na⁺/H⁺ exchanger 1 (NHE1) - calmodulin complexes of varying stoichiometry and structure regulate Ca²⁺-dependent NHE1 activation[J]. Elife,2021,10:e60889. doi: 10.7554/eLife.60889
[30]	Escudero D S,Pérez N G,Díaz R G. Myocardial impact of NHE1 regulation by sildenafil[J]. Front Cardiovasc Med,2021,8:617519. doi: 10.3389/fcvm.2021.617519
[31]	Suleiman M,Abdulrahman N,Yalcin H,et al. The role of CD44,hyaluronan and NHE1 in cardiac remodeling[J]. Life Sci,2018,209:197-201. doi: 10.1016/j.lfs.2018.08.009
[32]	Mohamed I A,Mraiche F. Targeting osteopontin,the silent partner of Na⁺/H⁺ exchanger isoform 1 in cardiac remodeling[J]. J Cell Physiol,2015,230(9):2006-2018. doi: 10.1002/jcp.24958
[33]	Previtali S C,Gidaro T,Díaz-Manera J,et al. Rimeporide as a ﬁrst- in-class NHE-1 inhibitor: Results of a phase Ib trial in young patients with duchenne muscular dystrophy[J]. Pharmacol Res,2020,159:104999. doi: 10.1016/j.phrs.2020.104999
[34]	Chen J,Chen S,Zhang B,et al. SIRT3 as a potential therapeutic target for heart failure[J]. Pharmacol Res,2021,165:105432. doi: 10.1016/j.phrs.2021.105432
[35]	He X,Zeng H,Chen J X. Emerging role of SIRT3 in endothelial metabolism,angiogenesis,and cardiovascular disease[J]. J Cell Physiol,2019,234(3):2252-2265. doi: 10.1002/jcp.27200
[36]	Chen W J,Cheng Y,Li W,et al. Quercetin attenuates cardiac hypertrophy by inhibiting mitochondrial dysfunction through SIRT3/PARP-1 pathway[J]. Front Pharmacol,2021,12:739615. doi: 10.3389/fphar.2021.739615
[37]	Liu J,Tang M,Li T,et al. Honokiol ameliorates post-myocardial infarction heart failure through Ucp3-mediated reactive oxygen species inhibition[J]. Front Pharmacol,2022,13:811682. doi: 10.3389/fphar.2022.811682
[38]	Pillai V B,Samant S,Sundaresan N R,et al. Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial SIRT3[J]. Nat Commun,2015,6:6656. doi: 10.1038/ncomms7656
[39]	马斌,雷贺吉,韩淑伟. 血清肿瘤坏死因子-α、白细胞介素-1β及白细胞介素-6与慢性心力衰竭病人心功能的相关性分析[J]. 中西医结合心脑血管病杂志,2019,17(16):2490-2492. doi: 10.12102/j.issn.1672-1349.2019.16.025
[40]	Hanna A,Frangogiannis N G. Inflammatory cytokines and chemokines as therapeutic targets in heart failure[J]. Cardiovasc Drugs Ther,2020,34(6):849-863. doi: 10.1007/s10557-020-07071-0
[41]	NemecSvete A,Verk B,Čebulj-Kadunc N,et al. Inflammation and its association with oxidative stress in dogs with heart failure[J]. BMC Vet Res,2021,17(1):176. doi: 10.1186/s12917-021-02878-x
[42]	Kotyla P J. Bimodal function of Anti-TNF treatment: shall we be concerned about Anti-TNF treatment in patients with rheumatoid arthritis and heart failure?[J]. Int J Mol Sci,2018,19(6):1739. doi: 10.3390/ijms19061739
[43]	Dinarello C A. The IL-1 family of cytokines and receptors in rheumatic diseases[J]. Nat Rev Rheumatol,2019,15(10):612-632. doi: 10.1038/s41584-019-0277-8
[44]	Abbate A,Toldo S,Marchetti C,et al. Interleukin-1 and the inflammasome as therapeutic targets in cardiovascular disease[J]. Circ Res,2020,126(9):1260-1280. doi: 10.1161/CIRCRESAHA.120.315937
[45]	Everett B M,Cornel J H,Lainscak M,et al. Anti-Inflammatory therapy with canakinumab for the prevention of hospitalization for heart failure[J]. Circulation,2019,139(10):1289-1299. doi: 10.1161/CIRCULATIONAHA.118.038010
[46]	Szekely Y,Arbel Y. A review of interleukin-1 in heart disease: Where do we stand today?[J]. Cardiol Ther,2018,7(1):25-44.
[47]	Ye Y,Yang X,Long B,et al. Association between a CCL17 genetic variant and risk of coronary artery disease in a Chinese Han population[J]. Circ J,2017,82(1):224-231.
[48]	Zhang Y,Ye Y,Tang X,et al. CCL17 acts as a novel therapeutic target in pathological cardiac hypertrophy and heart failure[J]. J Exp Med,2022,219(8):e20200418. doi: 10.1084/jem.20200418
[49]	Feng G,Bajpai G,Ma P,et al. CCL17 aggravates myocardial injury by suppressing recruitment of regulatory T cells[J]. Circulation,2022,145(10):765-782. doi: 10.1161/CIRCULATIONAHA.121.055888
[50]	Feng G,Zhu C,Lin C Y,et al. CCL17 protects against viral myocarditis by suppressing the recruitment of regulatory T cells[J]. J Am Heart Assoc,2023,12(4):e028442. doi: 10.1161/JAHA.122.028442

相关文章(20)

[1]	张海行, 张敬云, 许丹丹, 曹路, 李晶晶. miR-23通过调控PI3K/AKT/mTOR通路改善高血压性心力衰竭大鼠心肌血管生成的机制, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20251105
[2]	刘珍珍, 张迎, 高鑫宇. 血浆ADAMTS13水平与心力衰竭合并2型糖尿病患者临床预后的关系, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20250713
[3]	徐倩如, 董松武, 江荣炎. 沙库巴曲缬沙坦治疗冠状动脉疾病合并心力衰竭患者的疗效, 昆明医科大学学报.
[4]	李双秀, 郑琦, 尹高生, 杨萍, 凌露. 自噬通量受损介导细胞凋亡在压力负荷诱导心力衰竭中的作用, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20250906
[5]	董丹红, 王维雯, 李德霞, 杨军, 李娜, 马航, 李琳. 慢性射血分数降低的心力衰竭患者药物治疗现状云南单中心调查分析, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20230822
[6]	邱燕, 王引利, 杨萌萌, 郭良敏, 袁龙会. 肺动脉高压患者MPV、PDW和PCT水平与心功能的关系, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20231219
[7]	谢芹, 赵春阳, 张葆溯, 赵洪波. 硫利达嗪抗宫颈癌的潜在作用机制, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20220317
[8]	梅松, 蒋雯, 白向锋, 王文杰, 黄丹, 曹伟. 左西孟旦治疗重症冠心病所致心衰的临床疗效, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210121
[9]	宿玮洁, 张美沙, 李佳凝, 刘颖, 徐丁洁, 常宏. Ang Ⅱ诱导大鼠成肌细胞萎缩模型的构建, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20211026
[10]	李杰, 张施明, 杨淑莲. 抗氧化应激对慢性心力衰竭患者CysC及Pro-BNP的影响及相关性, 昆明医科大学学报.
[11]	章体玲, 张伟华, 罗庆祎, 夏洪颖, 鲁一兵. 沙库巴曲缬沙坦治疗扩张型心肌病心力衰竭的疗效, 昆明医科大学学报.
[12]	苏建培, 田伟盟, 顾俊, 何弥玉. C反应蛋白/白蛋白比值与老年心力衰竭患者长期预后的关系, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20201236
[13]	宋飞, 向盈盈, 毛志坚, 张小文. 2种不同方法制备的紫杉醇壳聚糖缓释膜的药物缓释特性对比, 昆明医科大学学报.
[14]	叶学群, 聂磊. 超声心动图结合动态心电图诊断冠心病合并心力衰竭的价值, 昆明医科大学学报.
[15]	李燕萍. 射血分数保留的心力衰竭临床特征, 昆明医科大学学报.
[16]	袁华苑. 慢性心力衰竭2 106例药物治疗分析, 昆明医科大学学报.
[17]	丁成彦. 超声新技术在慢性心衰心脏同步性检测中的临床应用, 昆明医科大学学报.
[18]	戴海龙. 超声新技术指导下心脏再同步化治疗心功能及相关因子水平观察, 昆明医科大学学报.
[19]	常颂桔. 尿酸干预对老年高血压合并糖尿病患者心功能的影响, 昆明医科大学学报.
[20]	黄永坤. 中药马蹄香和5种治疗胃肠病药物中的低聚糖含量测定和分析, 昆明医科大学学报.