Research Progress on the Role of Toll-like Receptor 7 in Cardiovascular Diseases

doi:10.19586/j.2095-2341.2024.0152

Current Biotechnology ›› 2025, Vol. 15 ›› Issue (2): 247-253.DOI: 10.19586/j.2095-2341.2024.0152

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Research Progress on the Role of Toll-like Receptor 7 in Cardiovascular Diseases

Ruoliu ZHANG¹^,²(), Mingwei BAO¹^,²()

^1.Department of Cardiology，Renmin Hospital of Wuhan University，Wuhan 430060，China
^2.Hubei Key Laboratory of Cardiology，Cardiovascular Research Institute of Wuhan University，Wuhan 430060，China

Received:2024-09-18 Accepted:2024-12-30 Online:2025-03-25 Published:2025-04-29
Contact: Mingwei BAO

Toll样受体7在心血管疾病中的作用研究进展

张若柳¹^,²(), 包明威¹^,²()

^1.武汉大学人民医院心血管内科，武汉 430060
^2.武汉大学心血管病研究所，心血管病湖北省重点实验室，武汉 430060

通讯作者: 包明威
作者简介:张若柳 E-mail: zhangrl5216@163.com；
基金资助:
国家自然科学基金项目(81970438)

Abstract

Abstract:

Cardiovascular disease is a type of disease with high incidence, disability, and mortality rates, which seriously threatens human health and imposes a huge economic and health burden on society. At present, there are countless studies on cardiovascular diseases, but the pathogenesis is still unclear. The involvement of TLRs in the occurrence and development of chronic inflammation in cardiovascular disease has been supported by experimental and preclinical data. Toll like receptor 7 (TLR7), as a key member of TLRs, can recognize bacterial, viral sources, and its own nucleic acids, and activate inflammatory responses through the myeloid differentiation factor 88 (MyD88) pathway to mediate immune responses. This review summarized the research progress of TLR7 in cardiovascular diseases such as atherosclerosis, myocarditis and cardiomyopathy, hypertension and pulmonary hypertension, and its potential as a drug target for cardiovascular diseases, in order to provide new ideas for clinical treatment of diseases.

Key words: Toll-like receptor 7, cardiovascular diseases, innate immunity, inflammation

摘要：

心血管疾病是一类具有高患病率、高致残率、高死亡率的疾病，严重威胁人类健康，对社会造成巨大的经济及卫生负担。目前针对心血管疾病的研究较多，但其发病机制尚不清楚。TLRs参与心血管疾病慢性炎症的发生发展得到了实验和临床前数据的支持。Toll样受体7（toll-like receptor 7，TLR7）作为TLRs的关键成员，可识别细菌、病毒来源以及自身的核酸，并通过髓样分化因子88 （myeloid differentiation factor 88，MyD88）途径激活炎症反应从而介导免疫应答。综述总结了TLR7在动脉粥样硬化、心肌炎与心肌病、高血压和肺动脉高压等心血管疾病中的研究进展及其作为治疗心血管疾病药物靶点的潜力，以期为疾病的临床治疗提供新思路。

关键词: Toll样受体7, 心血管疾病, 先天免疫, 炎症

CLC Number:

Ruoliu ZHANG, Mingwei BAO. Research Progress on the Role of Toll-like Receptor 7 in Cardiovascular Diseases[J]. Current Biotechnology, 2025, 15(2): 247-253.

张若柳, 包明威. Toll样受体7在心血管疾病中的作用研究进展[J]. 生物技术进展, 2025, 15(2): 247-253.

References 61

1	VOS T, LIM S S, ABBAFATI C, et al.. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the global burden of disease study 2019[J]. Lancet, 2020, 396(10258): 1204-1222.
2	National Center For Cardiovascular Diseases The Writing Committee Of The Report On Cardiovascular Health And Diseases In China. Report on cardiovascular health and diseases in China 2023: an updated summary[J]. Biomed. Environ. Sci., 2024, 37(9): 949-992.
3	HAMADE H, TSUDA M, OSHIMA N, et al.. Toll-like receptor 7 protects against intestinal inflammation and restricts the development of colonic tissue-resident memory CD8⁺ T cells[J/OL]. Front. Immunol., 2024, 15: 1465175[2025-02-17]. .
4	MAZZARINO M, CETIN E, BARTOSOVA M, et al.. Therapeutic targeting of chronic kidney disease-associated DAMPs differentially contributing to vascular pathology[J/OL]. Front. Immunol., 2023, 14: 1240679[2025-02-17]. .
5	段兴鹏,刘景丽,王澈,等.巨噬细胞清道夫受体与Toll样受体对Ox-LDL摄取和炎症的影响[J].生物技术进展,2024,14(4):668-675.
	DUAN X P, LIU J L, WANG C, et al.. Effects of macrophage scavenger receptors and toll-like receptors on OxLDL uptake and inflammation[J]. Curr. Biotechnol., 2024, 14(4): 668-675.
6	Correction to: unravelling the heart's comic drama: can TLRs and hyaluronan metabolism stoke neutrophil rage in acute coronary syndrome?‍[J/OL]. Eur. Heart J., 2023, 44(47): 4964[2025-02-17]. .
7	CHEN L, TANG W, LIU J, et al.. On-demand reprogramming of immunosuppressive microenvironment in tumor tissue via multi-regulation of carcinogenic microRNAs and RNAs dependent photothermal-immunotherapy using engineered gold nanoparticles for malignant tumor treatment[J/OL]. Biomaterials, 2025, 315: 122956[2025-02-17]. .
8	AN S, OH J, JSHON H, et al.. Co-adjuvanting Nod2-stimulating bacteria with a TLR7 agonist elicits potent protective immunity against respiratory virus infection[J/OL]. Int. J. Antimicrob. Agents, 2024, 64(6): 107369[2025-02-17]. .
9	PUNNANITINONT A, BISWAS S, KASPEREK E M, et al.. Tlr7 drives sex- and tissue-dependent effects in Sjögren's disease[J/OL]. Front. Cell Dev. Biol., 2024, 12: 1434269[2025-02-17]. .
10	SALVI V, GAUDENZI C, MARIOTTI B, et al.. Cell damage shifts the microRNA content of small extracellular vesicles into a Toll-like receptor 7-activating cargo capable to propagate inflammation and immunity[J/OL]. Cell Commun. Signal., 2024, 22(1): 536[2025-02-17]. .
11	MEDZHITOV R, PRESTON-HURLBURT P, JANEWAY C A. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity[J]. Nature, 1997, 388(6640): 394-397.
12	POLTORAK A, HE X, SMIRNOVA I, et al.. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene[J]. Science, 1998, 282(5396): 2085-2088.
13	WICHERSKA-PAWŁOWSKA K, WRÓBEL T, RYBKA J. Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs) in innate immunity. TLRs, NLRs, and RLRs ligands as immunotherapeutic agents for hematopoietic diseases[J/OL]. Int. J. Mol. Sci., 2021, 22(24): 13397[2025-02-17]. .
14	GHOSH S K, SAHA B, BANERJEE R. Insight into the sequence-structure relationship of TLR cytoplasm's toll/interleukin-1 receptor domain towards understanding the conserved functionality of TLR2 heterodimer in mammals[J]. J. Biomol. Struct. Dyn., 2021, 39(15): 5348-5357.
15	FITZGERALD K A, KAGAN J C. Toll-like receptors and the control of immunity[J]. Cell, 2020, 180(6): 1044-1066.
16	ZHOU R, LIU L, WANG Y. Viral proteins recognized by different TLRs[J]. J. Med. Virol., 2021, 93(11): 6116-6123.
17	HE L, HAN G, WU S, et al.. Toll-like receptor 7 contributes to neuropathic pain by activating NF-κB in primary sensory neurons[J]. Brain Behav. Immun., 2020, 87: 840-851.
18	PELKA K, BERTHELOOT D, REIMER E, et al.. The chaperone UNC93B1 regulates toll-like receptor stability independently of endosomal TLR transport[J]. Immunity, 2018, 48(5): 911-922.
19	MAJER O, LIU B, KREUK L S M, et al.. UNC93B1 recruits syntenin-1 to dampen TLR7 signalling and prevent autoimmunity[J]. Nature, 2019, 575(7782): 366-370.
20	DAVID C, ARANGO-FRANCO C A, BADONYI M, et al.. Gain-of-function human UNC93B1 variants cause systemic lupus erythematosus and chilblain lupus[J/OL]. J. Exp. Med., 2024, 221(8): e20232066[2025-02-17]. .
21	GOSWAMI R, NABAWY A, JIANG M, et al.. All-natural gelatin-based nanoemulsion loaded with TLR7/8 agonist for efficient modulation of macrophage polarization for immunotherapy[J/OL]. Nanomaterials, 2024, 14(19): 1556[2025-02-17]. .
22	DE GROOT N G, BONTROP R E. COVID-19 pandemic: is a gender-defined dosage effect responsible for the high mortality rate among males?[J]. Immunogenetics, 2020, 72(5): 275-277.
23	MISHRA H, SCHLACK-LEIGERS C, LIM E L, et al.. Disrupted degradative sorting of TLR7 is associated with human lupus[J/OL]. Sci. Immunol., 2024, 9(92): eadi9575[2025-02-17]. .
24	BROWN G J, CAÑETE P F, WANG H, et al.. TLR7 gain-of-function genetic variation causes human lupus[J]. Nature, 2022, 605(7909): 349-356.
25	MCCROREY M K, HAWKINS K P, SEMENIKHINA M, et al.. A novel preclinical murine model of systemic lupus erythematosus-like cardiovascular disease[J]. ACR Open Rheumatol., 2024, 6(12): 891-899.
26	YOKOGAWA M, TAKAISHI M, NAKAJIMA K, et al.. Epicutaneous application of toll-like receptor 7 agonists leads to systemic autoimmunity in wild-type mice: a new model of systemic lupus erythematosus[J]. Arthritis Rheumatol., 2014, 66(3): 694-706.
27	ZHANG Y, CUI H, ZHAO M, et al.. Cardiomyocyte-derived small extracellular vesicle-transported let-7b-5p modulates cardiac remodeling via TLR7 signaling pathway[J/OL]. FASEB J., 2024, 38(22): e70196[2025-02-17]. .
28	KROGMANN AO, LÜSEBRINK E, LAHRMANN C, et al.. Toll-like receptor 7 stimulation promotes the development of atherosclerosis in apolipoprotein E-deficient mice[J]. Int. Heart J., 2020, 61(2): 364-372.
29	KARPER J C, EWING M M, HABETS K L L, et al.. Blocking Toll-like receptors 7 and 9 reduces postinterventional remodeling via reduced macrophage activation, foam cell formation, and migration[J]. Arterioscler. Thromb. Vasc. Biol., 2012, 32(8): 72-80.
30	SALAGIANNI M, GALANI I E, LUNDBERG A M, et al.. Toll-like receptor 7 protects from atherosclerosis by constraining "inflammatory" macrophage activation[J]. Circulation, 2012, 126(8): 952-962.
31	KARADIMOU G, FOLKERSEN L, BERG M, et al.. Low TLR7 gene expression in atherosclerotic plaques is associated with major adverse cardio- and cerebrovascular events[J]. Cardiovasc. Res., 2017, 113(1): 30-39.
32	KARADIMOU G, GISTERÅ A, GALLINA A L, et al.. Treatment with a Toll-like receptor 7 ligand evokes protective immunity against atherosclerosis in hypercholesterolaemic mice[J]. J. Intern. Med., 2020, 288(3): 321-334.
33	ZHANG Y, ZHOU X, CHEN S, et al.. Immune mechanisms of group B coxsackievirus induced viral myocarditis[J/OL]. Virulence, 2023, 14(1): 2180951[2025-02-17]. .
34	JIANG Z, LI Z, CHEN Y, et al.. MLN4924 alleviates autoimmune myocarditis by promoting Act1 degradation and blocking Act1-mediated mRNA stability[J/OL]. Int. Immunopharmacol., 2024, 139: 112716[2025-02-17]. .
35	PEREZ-SHIBAYAMA C, GIL-CRUZ C, CADOSCH N, et al.. Bone morphogenic protein-4 availability in the cardiac microenvironment controls inflammation and fibrosis in autoimmune myocarditis[J]. Nat. Cardiovasc. Res., 2024, 3(3): 301-316.
36	HASHAM M G, BAXAN N, STUCKEY D J, et al.. Systemic autoimmunity induced by the TLR7/8 agonist resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease[J]. Dis. Model. Mech., 2017, 10(3): 259-270.
37	FUSE K, CHAN G, LIU Y, et al.. Myeloid differentiation factor-88 plays a crucial role in the pathogenesis of coxsackievirus B3-induced myocarditis and influences type I interferon production[J]. Circulation, 2005, 112(15): 2276-2285.
38	PAGNI P P, TRAUB S, DEMARIA O, et al.. Contribution of TLR7 and TLR9 signaling to the susceptibility of MyD88-deficient mice to myocarditis[J]. Autoimmunity, 2010, 43(4): 275-287.
39	VON HOFSTEN S, FENTON K A, PEDERSEN H L. Human and murine toll-like receptor-driven disease in systemic lupus erythematosus[J/OL]. Int. J. Mol. Sci., 2024, 25(10): 5351[2025-02-17]. .
40	MOLEÓN J, GONZÁLEZ-CORREA C, MIÑANO S, et al.. Protective effect of microbiota-derived short chain fatty acids on vascular dysfunction in mice with systemic lupus erythematosus induced by toll like receptor 7 activation[J/OL]. Pharmacol. Res., 2023, 198: 106997[2025-02-17]. .
41	CHAUDHARI S, D'SOUZA B M, MORALES J Y, et al.. Renal TLR-7/TNF-α pathway as a potential female-specific mechanism in the pathogenesis of autoimmune-induced hypertension[J]. Am. J. Physiol. Heart Circ. Physiol., 2022, 323(6): 1331-1342.
42	GONZÁLEZ-CORREA C, MOLEÓN J, MIÑANO S, et al.. Trimethylamine N-oxide promotes autoimmunity and a loss of vascular function in toll-like receptor 7-driven lupus mice[J/OL]. Antioxidants, 2021, 11(1): 84[2025-02-17]. .
43	ROBLES-VERA I, VISITACIÓN N D L, TORAL M, et al.. Toll-like receptor 7-driven lupus autoimmunity induces hypertension and vascular alterations in mice[J]. J. Hypertens., 2020, 38(7): 1322-1335.
44	DE LA VISITACIÓN N, ROBLES-VERA I, MOLEÓN J, et al.. Gut microbiota has a crucial role in the development of hypertension and vascular dysfunction in toll-like receptor 7-driven lupus autoimmunity[J/OL]. Antioxidants, 2021, 10(9): 1426[2025-02-17]. .
45	DE LA VISITACIÓN N, ROBLES-VERA I, MOLEÓN-MOYA J, et al.. Probiotics prevent hypertension in a murine model of systemic lupus erythematosus induced by toll-like receptor 7 activation[J/OL]. Nutrients, 2021, 13(8): 2669[2025-02-17]. .
46	CHATTERJEE P, CHIASSON V L, PINZUR L, et al.. Human placenta-derived stromal cells decrease inflammation, placental injury and blood pressure in hypertensive pregnant mice[J]. Clin. Sci., 2016, 130(7): 513-523.
47	HARWANI S C, CHAPLEAU M W, LEGGE K L, et al.. Neurohormonal modulation of the innate immune system is proinflammatory in the prehypertensive spontaneously hypertensive rat, a genetic model of essential hypertension[J]. Circ. Res., 2012, 111(9): 1190-1197.
48	KARIOTIS S, JAMMEH E, SWIETLIK E M, et al.. Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood[J/OL]. Nat. Commun., 2021, 12(1): 7104[2025-02-17]. .
49	JONES R J, DE BIE E M D D, GROVES E, et al.. Autoimmunity is a significant feature of idiopathic pulmonary arterial hypertension[J]. Am. J. Respir. Crit. Care Med., 2022, 206(1): 81-93.
50	RHEE R L, GABLER N B, SANGANI S, et al.. Comparison of treatment response in idiopathic and connective tissue disease-associated pulmonary arterial hypertension[J]. Am. J. Respir. Crit. Care Med., 2015, 192(9): 1111-1117.
51	YEH F C, CHEN C N, XIE C Y, et al.. TLR7/8 activation induces autoimmune vasculopathy and causes severe pulmonary arterial hypertension[J/OL]. Eur. Respir. J., 2023, 62(1): 2300204[2025-02-17]. .
52	ZHANG L, ZENG X X, LI Y M, et al.. Keratin 1 attenuates hypoxic pulmonary artery hypertension by suppressing pulmonary artery media smooth muscle expansion[J/OL]. Acta Physiol., 2021, 231(2): e13558[2025-02-17]. .
53	WANG J, CHEN J, SHU L, et al.. Carotid baroreceptor stimulation improves pulmonary arterial remodeling and right ventricular dysfunction in pulmonary arterial hypertension[J]. JACC Basic Transl. Sci., 2024, 9(4): 475-492.
54	TOJO S, ZHANG Z, MATSUI H, et al.. Structural analysis reveals TLR7 dynamics underlying antagonism[J/OL]. Nat. Commun., 2020, 11(1): 5204[2025-02-17]. .
55	HEMMI H, KAISHO T, TAKEUCHI O, et al.. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway[J]. Nat. Immunol., 2002, 3(2): 196-200.
56	ABT M C, BUFFIE C G, SUŠAC B, et al.. TLR-7 activation enhances IL-22-mediated colonization resistance against vancomycin-resistant Enterococcus [J/OL]. Sci. Transl. Med., 2016, 8(327): 327ra25[2025-02-17]. .
57	SUN H, LI Y, ZHANG P, et al.. Targeting toll-like receptor 7/8 for immunotherapy: recent advances and prospectives[J/OL]. Biomark. Res., 2022, 10(1): 89[2025-02-17]. .
58	QI S, ZHANG X, YU X, et al.. Supramolecular lipid nanoparticles based on host-guest recognition: a new generation delivery system of mRNA vaccines for cancer immunotherapy[J/OL]. Adv. Mater., 2024, 36(23): e2311574[2025-02-17]. .
59	LAI C Y, SU Y W, LIN K I, et al.. Natural modulators of endosomal toll-like receptor-mediated psoriatic skin inflammation[J/OL]. J. Immunol. Res., 2017, 2017: 7807313[2025-02-17]. .
60	CENAC C, DUCATEZ M F, CGUÉRY J. Hydroxychloroquine inhibits proteolytic processing of endogenous TLR7 protein in human primary plasmacytoid dendritic cells[J]. Eur. J. Immunol., 2022, 52(1): 54-61.
61	PORT A, SHAW J V, KLOPP-SCHULZE L, et al.. Phase 1 study in healthy participants of the safety, pharmacokinetics, and pharmacodynamics of enpatoran (M5049), a dual antagonist of toll-like receptors 7 and 8[J/OL]. Pharmacol. Res. Perspect., 2021, 9(5): e00842[2025-02-17]. .

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Research Progress on the Role of Toll-like Receptor 7 in Cardiovascular Diseases

Toll样受体7在心血管疾病中的作用研究进展

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