Potential Therapeutic Strategies for Myocardial Infarction: the Role of Toll-like Receptors

Overview

Journal Immunol Res

Specialty Allergy & Immunology

Date 2022 May 24

PMID 35608723

Authors

Sumra Komal

Nimrah Komal

Ali Mujtaba

Shu-Hui Wang

Li-Rong Zhang

Sheng-Na Han

Affiliations

Soon will be listed here.

Abstract

Myocardial infarction (MI) is a life-threatening condition among patients with cardiovascular diseases. MI increases the risk of stroke and heart failure and is a leading cause of morbidity and mortality worldwide. Several genetic and epigenetic factors contribute to the development of MI, suggesting that further understanding of the pathomechanism of MI might help in the early management and treatment of this disease. Toll-like receptors (TLRs) are well-known members of the pattern recognition receptor (PRR) family and contribute to both adaptive and innate immunity. Collectively, studies suggest that TLRs have a cardioprotective effect. However, prolonged TLR activation in the response to signals generated by damage-associated molecular patterns (DAMPs) results in the release of inflammatory cytokines and contributes to the development and exacerbation of myocardial inflammation, MI, ischemia-reperfusion injury, myocarditis, and heart failure. The objective of this review is to discuss and summarize the association of TLRs with MI, highlighting their therapeutic potential for the development of advanced TLR-targeted therapies for MI.

Citing Articles

The therapeutic potential of Honeysuckle in cardiovascular disease: an anti-inflammatory intervention strategy.

Zhao Y, Zhang J, Lu F, Xu W, Ma Q, Hu J Am J Transl Res. 2025; 16(12):7262-7277.

PMID: 39822489 PMC: 11733370. DOI: 10.62347/NJMJ7853.

Chinese medicine in the treatment of chronic hepatitis B: The mechanisms of signal pathway regulation.

Zheng S, Qi W, Xue T, Zao X, Xie J, Zhang P Heliyon. 2024; 10(20):e39176.

PMID: 39640799 PMC: 11620126. DOI: 10.1016/j.heliyon.2024.e39176.

TBC1 domain family member 25 protects against myocardial apoptosis and the proinflammatory response triggered by ischemia-reperfusion injury through suppression of the TAK1-JNK/p38 MAPK signaling cascade.

Liu Z, Shang F, Li N, Dong W In Vitro Cell Dev Biol Anim. 2023; 59(10):796-810.

PMID: 38100060 DOI: 10.1007/s11626-023-00826-7.

Identification of Key Immune-Related Genes in the Treatment of Heart Failure After Myocardial Infarction with Empagliflozin Based on RNA-Seq.

Zhang P, Wang T, Luo Z, Ding J, Yang Q, Hu P J Inflamm Res. 2023; 16:4679-4696.

PMID: 37872957 PMC: 10590601. DOI: 10.2147/JIR.S428747.

Epigenetic Regulation of Macrophage Polarization in Cardiovascular Diseases.

Komal S, Han S, Cui L, Zhai M, Zhou Y, Wang P Pharmaceuticals (Basel). 2023; 16(2).

PMID: 37259293 PMC: 9963081. DOI: 10.3390/ph16020141.

References

Mendis S, Thygesen K, Kuulasmaa K, Giampaoli S, Mahonen M, Blackett K . World Health Organization definition of myocardial infarction: 2008-09 revision. Int J Epidemiol. 2010; 40(1):139-46. DOI: 10.1093/ije/dyq165. View

Havranek E, Mujahid M, Barr D, Blair I, Cohen M, Cruz-Flores S . Social Determinants of Risk and Outcomes for Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2015; 132(9):873-98. DOI: 10.1161/CIR.0000000000000228. View

Benjamin E, Blaha M, Chiuve S, Cushman M, Das S, Deo R . Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017; 135(10):e146-e603. PMC: 5408160. DOI: 10.1161/CIR.0000000000000485. View

Kim H, Kim J, Woo J, Park C, Cho J, Lee S . Circadian Distribution of Acute Myocardial Infarction in Different Age Groups. Am J Cardiol. 2018; 121(11):1279-1284. DOI: 10.1016/j.amjcard.2018.02.006. View

Arnett D, Blumenthal R, Albert M, Buroker A, Goldberger Z, Hahn E . 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019; 74(10):e177-e232. PMC: 7685565. DOI: 10.1016/j.jacc.2019.03.010. View

Gianfagna F, Cugino D, Santimone I, Iacoviello L . From candidate gene to genome-wide association studies in cardiovascular disease. Thromb Res. 2011; 129(3):320-4. DOI: 10.1016/j.thromres.2011.11.014. View

Yamada Y, Kato K, Oguri M, Horibe H, Fujimaki T, Yasukochi Y . Identification of 13 novel susceptibility loci for early-onset myocardial infarction, hypertension, or chronic kidney disease. Int J Mol Med. 2018; 42(5):2415-2436. PMC: 6192728. DOI: 10.3892/ijmm.2018.3852. View

Bagai A, Dangas G, Stone G, Granger C . Reperfusion strategies in acute coronary syndromes. Circ Res. 2014; 114(12):1918-28. DOI: 10.1161/CIRCRESAHA.114.302744. View

Bougouin W, Marijon E, Puymirat E, Defaye P, Celermajer D, Le Heuzey J . Incidence of sudden cardiac death after ventricular fibrillation complicating acute myocardial infarction: a 5-year cause-of-death analysis of the FAST-MI 2005 registry. Eur Heart J. 2013; 35(2):116-22. DOI: 10.1093/eurheartj/eht453. View

10.

Bu D, Su Z, Zou J, Meng M, Wang C . Study of the mechanism underlying therapeutic effect of Compound Longmaining on myocardial infarction using a network pharmacology-based approach. Biomed Pharmacother. 2019; 118:109234. DOI: 10.1016/j.biopha.2019.109234. View

11.

Lemaitre B, Nicolas E, Michaut L, Reichhart J, Hoffmann J . The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996; 86(6):973-83. DOI: 10.1016/s0092-8674(00)80172-5. View

12.

Kawai T, Akira S . The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010; 11(5):373-84. DOI: 10.1038/ni.1863. View

13.

Li M, Carpio D, Zheng Y, Bruzzo P, Singh V, Ouaaz F . An essential role of the NF-kappa B/Toll-like receptor pathway in induction of inflammatory and tissue-repair gene expression by necrotic cells. J Immunol. 2001; 166(12):7128-35. DOI: 10.4049/jimmunol.166.12.7128. View

14.

Viglianti G, Lau C, Hanley T, Miko B, Shlomchik M, Marshak-Rothstein A . Activation of autoreactive B cells by CpG dsDNA. Immunity. 2003; 19(6):837-47. DOI: 10.1016/s1074-7613(03)00323-6. View

15.

Lau C, Broughton C, Tabor A, Akira S, Flavell R, Mamula M . RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement. J Exp Med. 2005; 202(9):1171-7. PMC: 2213226. DOI: 10.1084/jem.20050630. View

16.

Cavassani K, Ishii M, Wen H, Schaller M, Lincoln P, Lukacs N . TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events. J Exp Med. 2008; 205(11):2609-21. PMC: 2571935. DOI: 10.1084/jem.20081370. View

17.

Sioud M . Innate sensing of self and non-self RNAs by Toll-like receptors. Trends Mol Med. 2006; 12(4):167-76. DOI: 10.1016/j.molmed.2006.02.004. View

18.

Vabulas R, Ahmad-Nejad P, da Costa C, Miethke T, Kirschning C, Hacker H . Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J Biol Chem. 2001; 276(33):31332-9. DOI: 10.1074/jbc.M103217200. View

19.

Vabulas R, Ahmad-Nejad P, Ghose S, Kirschning C, Issels R, Wagner H . HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J Biol Chem. 2002; 277(17):15107-12. DOI: 10.1074/jbc.M111204200. View

20.

Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A . Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2007; 13(9):1050-9. DOI: 10.1038/nm1622. View