Mechanism and Therapeutic Potential of Exosomes in Valvular Heart Disease
Research Article
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Mechanism and Therapeutic Potential of Exosomes in Valvular Heart Disease

Zhouyun Yao 1*
1 Harbin Medical University
*Corresponding author: 1824498395@qq.com
Published on 14 October 2025
Journal Cover
TNS Vol.141
ISSN (Print): 2753-8826
ISSN (Online): 2753-8818
ISBN (Print): 978-1-80590-395-6
ISBN (Online): 978-1-80590-396-3
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Abstract

Valvular heart disease (VHD), a category of diseases severely affecting circulatory system function caused by structural or functional abnormalities in heart valves, significantly reduces patients 'quality of life and life expectancy. Although pharmacological interventions and surgical procedures can alleviate clinical symptoms to some extent, achieving valve tissue regeneration and functional reconstruction remains challenging. In recent years, exosomes have gained widespread attention as an emerging therapeutic strategy. These nanoscale vesicles secreted by cells are rich in various bioactive components and play crucial roles in intercellular communication, inflammation regulation, tissue repair, and pathological process modulation. Studies indicate that during the development of cardiac valvular lesions, exosomes demonstrate significant therapeutic potential by regulating inflammatory responses, promoting tissue regeneration, and improving valve function. However, the specific mechanisms of exosomes in valvular disease treatment remain complex, with clinical translation facing multiple challenges including improvements in isolation and purification techniques, enhancement of in vivo stability, and systematic elucidation of action mechanisms. This systematic review examines the pathogenesis of valvular heart disease, discusses exosomes' biological characteristics and their potential as biomarkers and targeted therapies, while exploring current research progress and key scientific issues to provide theoretical foundations for further exploration and clinical application in this field.

Keywords:

valvular heart disease, exosomes, therapeutic targets, biomarkers

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Yao,Z. (2025). Mechanism and Therapeutic Potential of Exosomes in Valvular Heart Disease. Theoretical and Natural Science,141,37-45.

References

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References

[1]. Aluru JS, Barsouk A, Saginala K, Rawla P, Barsouk A. Valvular Heart Disease Epidemiology. Med Sci (Basel). 2022 Jun 15; 10(2): 32.

[2]. Kisling A, Gallagher R. Valvular Heart Disease. Prim Care. 2024 Mar; 51(1): 95-109.

[3]. David Messika-Zeitoun, Helmut Baumgartner, Ian G Burwash, Alec Vahanian, Jeroen Bax, Philippe Pibarot, Vince Chan, Martin Leon, Maurice Enriquez-Sarano, Thierry Mesana, Bernard Iung, Unmet needs in valvular heart disease, European Heart Journal, Volume 44, Issue 21, 1 June 2023, Pages 1862–1873

[4]. Doyle LM, Wang MZ. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells. 2019 Jul 15; 8(7): 727.

[5]. Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013 Feb 18; 200(4): 373-83.

[6]. Moghassemi S, Dadashzadeh A, Sousa MJ, Vlieghe H, Yang J, León-Félix CM, Amorim CA. Extracellular vesicles in nanomedicine and regenerative medicine: A review over the last decade. Bioact Mater. 2024 Mar 2; 36: 126-156. .

[7]. Kulus M, Farzaneh M, Sheykhi-Sabzehpoush M, Ghaedrahmati F, Mehravar F, Józkowiak M, Piotrowska-Kempisty H, Bukowska D, Antosik P, Podhorska-Okołów M, Zabel M, Mozdziak P, Dzięgiel P, Kempisty B. Exosomes and non-coding RNAs: Exploring their roles in human myocardial dysfunction. Biomed Pharmacother. 2025 Feb; 183: 117853.

[8]. Li J, Sun S, Zhu D, Mei X, Lyu Y, Huang K, Li Y, Liu S, Wang Z, Hu S, Lutz HJ, Popowski KD, Dinh PC, Butte AJ, Cheng K. Inhalable Stem Cell Exosomes Promote Heart Repair After Myocardial Infarction. Circulation. 2024 Aug 27; 150(9): 710-723.

[9]. Tao Shouqi. Etiology and Pathophysiology of Mitral Valve Disease [J]. Chinese Circulation Journal, 1990, (04): 274-275.

[10]. Di Gioia G, Bartunek J, Tesorio T, Vukcevic V, Aleksandric S, Dobric M, Franco D, Barbato E, Banovic M. Pathophysiology, Diagnosis, and Treatment of Patients with Concomitant Severe Aortic Stenosis and Coronary Artery Disease: A Closer Look to the Unresolved Perplexity. J Clin Med. 2021 Apr 11; 10(8): 1617..

[11]. Pibarot P, Dumesnil JG. New concepts in valvular hemodynamics: implications for diagnosis and treatment of aortic stenosis. Can J Cardiol. 2007 Oct; 23 Suppl B(Suppl B): 40B-47B.

[12]. Côté N, Simard L, Zenses AS, Tastet L, Shen M, Clisson M, Clavel MA. Impact of Vascular Hemodynamics on Aortic Stenosis Evaluation: New Insights Into the Pathophysiology of Normal Flow-Small Aortic Valve Area-Low Gradient Pattern. J Am Heart Assoc. 2017 Jul 7; 6(7): e006276.

[13]. Linhart JW, Hildner FJ, Barold SS, Samet P. The hemodynamic consequences of the acute development of aortic valvular insufficiency in man. J Thorac Cardiovasc Surg. 1969 Oct; 58(4): 592-600.

[14]. Baumbach A, Patel KP, Rudolph TK, Delgado V, Treede H, Tamm AR. Aortic regurgitation: from mechanisms to management. EuroIntervention. 2024 Sep 2; 20(17): e1062-e1075.

[15]. Unger P, Lancellotti P, Amzulescu M, David-Cojocariu A, de Cannière D. Pathophysiology and management of combined aortic and mitral regurgitation. Arch Cardiovasc Dis. 2019 Jun-Jul; 112(6-7): 430-440.

[16]. KAPLAN MH. The concept of autoantibodies in rheumatic fever and in the postcommissurotomy state. Ann N Y Acad Sci. 1960 Jun 30; 86: 974-91.

[17]. Passos LSA, Nunes MCP, Aikawa E. Rheumatic Heart Valve Disease Pathophysiology and Underlying Mechanisms. Front Cardiovasc Med. 2021 Jan 18; 7: 612716.

[18]. Raynes JM, Frost HR, Williamson DA, Young PG, Baker EN, Steemson JD, Loh JM, Proft T, Dunbar PR, Atatoa Carr PE, Bell A, Moreland NJ. Serological Evidence of Immune Priming by Group A Streptococci in Patients with Acute Rheumatic Fever. Front Microbiol. 2016 Jul 22; 7: 1119.

[19]. Passos LSA, Jha PK, Becker-Greene D, Blaser MC, Romero D, Lupieri A, Sukhova GK, Libby P, Singh SA, Dutra WO, Aikawa M, Levine RA, Nunes MCP, Aikawa E. Prothymosin Alpha: A Novel Contributor to Estradiol Receptor Alpha-Mediated CD8+ T-Cell Pathogenic Responses and Recognition of Type 1 Collagen in Rheumatic Heart Valve Disease. Circulation. 2022 Feb 15; 145(7): 531-548.

[20]. Kemeny E, Grieve T, Marcus R, Sareli P, Zabriskie JB. Identification of mononuclear cells and T cell subsets in rheumatic valvulitis. Clin Immunol Immunopathol. 1989 Aug; 52(2): 225-37.

[21]. Guilherme L, Cury P, Demarchi LM, Coelho V, Abel L, Lopez AP, Oshiro SE, Aliotti S, Cunha-Neto E, Pomerantzeff PM, Tanaka AC, Kalil J. Rheumatic heart disease: proinflammatory cytokines play a role in the progression and maintenance of valvular lesions. Am J Pathol. 2004 Nov; 165(5): 1583-91.

[22]. Hajishengallis G, Netea MG, Chavakis T. Trained immunity in chronic inflammatory diseases and cancer. Nat Rev Immunol. 2025 Jan 31.

[23]. Jiang Weijian, Fang Ming, Su Jinwen, et al. Effects and Mechanisms of MicroRNA-486 and TGF-β1 on Aortic Valve Calcification in Homo sapiens [J]. Chinese Journal of Modern Medicine, 2018, 28(32): 25-32.

[24]. Anilkumar S, Wright-Jin E. NF-κB as an Inducible Regulator of Inflammation in the Central Nervous System. Cells. 2024 Mar 11; 13(6): 485.

[25]. Dogan S, Kimyon G, Ozkan H, Kacmaz F, Camdeviren B, Karaaslan I. TNF-alpha, IL-6, IL-10 and fatty acids in rheumatoid arthritis patients receiving cDMARD and bDMARD therapy. Clin Rheumatol. 2022 Aug; 41(8): 2341-2349.

[26]. CHEN Shisong, HUANG Kai, XU Hongjie, XU Zhiyun, HAN Lin, LIU Xiaohong. Causal relationship between 91 inflammatory proteins and 5 cardiovascular diseases: a bidirectional Mendelian randomization. Academic Journal of Naval Medical University, 2024, 45(5): 558-568.

[27]. Small AM, Yutzey KE, Binstadt BA, Voigts Key K, Bouatia-Naji N, Milan D, Aikawa E, Otto CM, St Hilaire C; American Heart Association Council on Genomic and Precision Medicine; Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; and Council on Cardiovascular and Stroke Nursing. Unraveling the Mechanisms of Valvular Heart Disease to Identify Medical Therapy Targets: A Scientific Statement From the American Heart Association. Circulation. 2024 Aug 6; 150(6): e109-e128.

[28]. Martin M, Motta SE, Emmert MY. Have we found the missing link between inflammation, fibrosis, and calcification in calcific aortic valve disease? Eur Heart J. 2023 Mar 7; 44(10): 899-901.

[29]. Li F, Fang R, Rao L, Meng F, Zhao X. [Research progress on exosomes in diagnosis and treatment of cardiovascular diseases]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2018 May 25; 47(3): 320-326.

[30]. Zhang TR, Huang WQ. Angiogenic Exosome-Derived microRNAs: Emerging Roles in Cardiovascular Disease. J Cardiovasc Transl Res. 2021 Oct; 14(5): 824-840.

[31]. Pan Y, Wu W, Jiang X, Liu Y. Mesenchymal stem cell-derived exosomes in cardiovascular and cerebrovascular diseases: From mechanisms to therapy. Biomed Pharmacother. 2023 Jul; 163: 114817.

[32]. Bakhshian Nik A, Hutcheson JD, Aikawa E. Extracellular Vesicles As Mediators of Cardiovascular Calcification. Front Cardiovasc Med. 2017 Dec 11; 4: 78.

[33]. Wortzel I, Dror S, Kenific CM, Lyden D. Exosome-Mediated Metastasis: Communication from a Distance. Dev Cell. 2019 May 6; 49(3): 347-360.

[34]. Amrute JM, Luo X, Penna V, Yang S, Yamawaki T, Hayat S, Bredemeyer A, Jung IH, Kadyrov FF, Heo GS, Venkatesan R, Shi SY, Parvathaneni A, Koenig AL, Kuppe C, Baker C, Luehmann H, Jones C, Kopecky B, Zeng X, Bleckwehl T, Ma P, Lee P, Terada Y, Fu A, Furtado M, Kreisel D, Kovacs A, Stitziel NO, Jackson S, Li CM, Liu Y, Rosenthal NA, Kramann R, Ason B, Lavine KJ. Targeting immune-fibroblast cell communication in heart failure. Nature. 2024 Nov; 635(8038): 423-433.

[35]. Akhmerov A, Parimon T. Extracellular Vesicles, Inflammation, and Cardiovascular Disease. Cells. 2022 Jul 18; 11(14): 2229.

[36]. You Y, Tian Y, Guo R, Shi J, Kwak KJ, Tong Y, Estania AP, Hsu WH, Liu Y, Hu S, Cao J, Yang L, Bai R, Huang P, Lee LJ, Jiang W, Kim BYS, Ma S, Liu X, Shen Z, Lan F, Phuong Nguyen PK, Lee AS. Extracellular vesicle-mediated VEGF-A mRNA delivery rescues ischaemic injury with low immunogenicity. Eur Heart J. 2025 Jan 20: ehae883.

[37]. Zheng H, Liang X, Liu B, Huang X, Shen Y, Lin F, Chen J, Gao X, He H, Li W, Hu B, Li X, Zhang Y. Exosomal miR-9-5p derived from iPSC-MSCs ameliorates doxorubicin-induced cardiomyopathy by inhibiting cardiomyocyte senescence. J Nanobiotechnology. 2024 Apr 20; 22(1): 195.

[38]. Ma X, Liu B, Fan L, Liu Y, Zhao Y, Ren T, Li Y, Li Y. Native and engineered exosomes for inflammatory disease. Nano Res. 2023; 16(5): 6991-7006.

[39]. Greening DW, Gopal SK, Xu R, Simpson RJ, Chen W. Exosomes and their roles in immune regulation and cancer. Semin Cell Dev Biol. 2015 Apr; 40: 72-81.

[40]. Yu P, Han Y, Meng L, Tang Z, Jin Z, Zhang Z, Zhou Y, Luo J, Luo J, Han C, Zhang C, Kong L. The incorporation of acetylated LAP-TGF-β1 proteins into exosomes promotes TNBC cell dissemination in lung micro-metastasis. Mol Cancer. 2024 Apr 25; 23(1): 82.

[41]. Du YM, Zhuansun YX, Chen R, Lin L, Lin Y, Li JG. Mesenchymal stem cell exosomes promote immunosuppression of regulatory T cells in asthma. Exp Cell Res. 2018 Feb 1; 363(1): 114-120.

[42]. Meng WT, Zhu J, Wang YC, Shao CL, Li XY, Lu PP, Huang MY, Mou FF, Guo HD, Ji G. Targeting delivery of miR-146a via IMTP modified milk exosomes exerted cardioprotective effects by inhibiting NF-κB signaling pathway after myocardial ischemia-reperfusion injury. J Nanobiotechnology. 2024 Jul 1; 22(1): 382.

[43]. Zhang B, Yin Y, Lai RC, Tan SS, Choo AB, Lim SK. Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells Dev. 2014 Jun 1; 23(11): 1233-44.

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Cite this article

Yao,Z. (2025). Mechanism and Therapeutic Potential of Exosomes in Valvular Heart Disease. Theoretical and Natural Science,141,37-45.

Data availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

About volume

Volume title: Proceedings of ICBioMed 2025 Symposium: AI for Healthcare: Advanced Medical Data Analytics and Smart Rehabilitation

ISBN: 978-1-80590-395-6(Print) / 978-1-80590-396-3(Online)
Editor: Alan Wang
Conference website: https://2025.icbiomed.org/auckland.html
Conference date: 17 October 2025
Series: Theoretical and Natural Science
Volume number: Vol.141
ISSN: 2753-8818(Print) / 2753-8826(Online)

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