Potential Therapeutic Targets and Research Progress of Related Drugs of Heart Failure
-
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。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.
-
Key words:
- Heart failure /
- Target /
- Drug
-
[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
点击查看大图
计量
- 文章访问数: 3354
- HTML全文浏览量: 2253
- PDF下载量: 85
- 被引次数: 0