Exosomes in Atherosclerosis, a Double-Edged Sword: Their Role in Disease Pathogenesis and Their Potential As Novel Therapeutics

Overview

Journal AAPS J

Specialty Pharmacology

Date 2021 Jul 27

PMID 34312734

Citations 14

Authors

Neil Patel

Deborah D Chin

Eun Ji Chung

Affiliations

Soon will be listed here.

Abstract

Cardiovascular disease (CAD) due to atherosclerosis is a major cause of death worldwide. The development of atherosclerosis involves intercellular communication facilitated by exosomes secreted from vascular endothelial cells (VECs), vascular smooth muscle cells (VSMCs), immune cells, and platelets. In this review, we summarize the current understanding of exosome biogenesis and uptake, and discuss atherogenic and atheroprotective functions of exosomes secreted from these cell types. In addition, we examine the potential of enhancing the therapeutic and targeting ability of exosomes exhibiting atheroprotective function by drug loading and surface modification with targeting ligands. We conclude with current challenges associated with exosome engineering for therapeutic use.

Citing Articles

Engineered exosomes as a prospective therapy for diabetic foot ulcers.

Guo L, Xiao D, Xing H, Yang G, Yang X Burns Trauma. 2024; 12:tkae023.

PMID: 39026930 PMC: 11255484. DOI: 10.1093/burnst/tkae023.

Exosome nanovesicles: biomarkers and new strategies for treatment of human diseases.

Xu C, Jiang C, Li Z, Gao H, Xian J, Guo W MedComm (2020). 2024; 5(8):e660.

PMID: 39015555 PMC: 11247338. DOI: 10.1002/mco2.660.

Broader Perspective on Atherosclerosis-Selected Risk Factors, Biomarkers, and Therapeutic Approach.

Fularski P, Czarnik W, Dabek B, Lisinska W, Radzioch E, Witkowska A Int J Mol Sci. 2024; 25(10).

PMID: 38791250 PMC: 11121693. DOI: 10.3390/ijms25105212.

Exosomes derived from HUVECs alleviate ischemia-reperfusion induced inflammation in neural cells by upregulating KLF14 expression.

Qin J, Zhou L, Yu L, Ye J, Wang F, Zhou J Front Pharmacol. 2024; 15:1365928.

PMID: 38756375 PMC: 11096520. DOI: 10.3389/fphar.2024.1365928.

The Landscape of Exosomes Biogenesis to Clinical Applications.

Al-Madhagi H Int J Nanomedicine. 2024; 19:3657-3675.

PMID: 38681093 PMC: 11048319. DOI: 10.2147/IJN.S463296.

References

Benjamin E, Muntner P, Alonso A, Bittencourt M, Callaway C, Carson A . Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation. 2019; 139(10):e56-e528. DOI: 10.1161/CIR.0000000000000659. View

Bentzon J, Otsuka F, Virmani R, Falk E . Mechanisms of plaque formation and rupture. Circ Res. 2014; 114(12):1852-66. DOI: 10.1161/CIRCRESAHA.114.302721. View

Singh R, Mengi S, Xu Y, Arneja A, Dhalla N . Pathogenesis of atherosclerosis: A multifactorial process. Exp Clin Cardiol. 2009; 7(1):40-53. PMC: 2716189. View

Petsophonsakul P, Furmanik M, Forsythe R, Dweck M, Schurink G, Natour E . Role of Vascular Smooth Muscle Cell Phenotypic Switching and Calcification in Aortic Aneurysm Formation. Arterioscler Thromb Vasc Biol. 2019; 39(7):1351-1368. DOI: 10.1161/ATVBAHA.119.312787. View

Marx S, Totary-Jain H, Marks A . Vascular smooth muscle cell proliferation in restenosis. Circ Cardiovasc Interv. 2011; 4(1):104-11. PMC: 3816546. DOI: 10.1161/CIRCINTERVENTIONS.110.957332. View

Bennett M, Sinha S, Owens G . Vascular Smooth Muscle Cells in Atherosclerosis. Circ Res. 2016; 118(4):692-702. PMC: 4762053. DOI: 10.1161/CIRCRESAHA.115.306361. View

Basatemur G, Jorgensen H, Clarke M, Bennett M, Mallat Z . Vascular smooth muscle cells in atherosclerosis. Nat Rev Cardiol. 2019; 16(12):727-744. DOI: 10.1038/s41569-019-0227-9. View

Brophy M, Dong Y, Wu H, Rahman H, Song K, Chen H . Eating the Dead to Keep Atherosclerosis at Bay. Front Cardiovasc Med. 2017; 4:2. PMC: 5277199. DOI: 10.3389/fcvm.2017.00002. View

Niessner A, Sato K, Chaikof E, Colmegna I, Goronzy J, Weyand C . Pathogen-sensing plasmacytoid dendritic cells stimulate cytotoxic T-cell function in the atherosclerotic plaque through interferon-alpha. Circulation. 2006; 114(23):2482-9. DOI: 10.1161/CIRCULATIONAHA.106.642801. View

10.

Abedin M, Tintut Y, Demer L . Vascular calcification: mechanisms and clinical ramifications. Arterioscler Thromb Vasc Biol. 2004; 24(7):1161-70. DOI: 10.1161/01.ATV.0000133194.94939.42. View

11.

Badimon L, Vilahur G . Thrombosis formation on atherosclerotic lesions and plaque rupture. J Intern Med. 2014; 276(6):618-32. DOI: 10.1111/joim.12296. View

12.

Moore K, Tabas I . Macrophages in the pathogenesis of atherosclerosis. Cell. 2011; 145(3):341-55. PMC: 3111065. DOI: 10.1016/j.cell.2011.04.005. View

13.

Baruah J, Wary K . Exosomes in the Regulation of Vascular Endothelial Cell Regeneration. Front Cell Dev Biol. 2020; 7:353. PMC: 6962177. DOI: 10.3389/fcell.2019.00353. View

14.

Chen Y, Yuan H, Ou Z, Ou J . Microparticles (Exosomes) and Atherosclerosis. Curr Atheroscler Rep. 2020; 22(6):23. DOI: 10.1007/s11883-020-00841-z. View

15.

Kapustin A, Shanahan C . Emerging roles for vascular smooth muscle cell exosomes in calcification and coagulation. J Physiol. 2016; 594(11):2905-14. PMC: 4887700. DOI: 10.1113/JP271340. View

16.

Johnsen K, Gudbergsson J, Skov M, Pilgaard L, Moos T, Duroux M . A comprehensive overview of exosomes as drug delivery vehicles - endogenous nanocarriers for targeted cancer therapy. Biochim Biophys Acta. 2014; 1846(1):75-87. DOI: 10.1016/j.bbcan.2014.04.005. View

17.

Zappulli V, Friis K, Fitzpatrick Z, Maguire C, Breakefield X . Extracellular vesicles and intercellular communication within the nervous system. J Clin Invest. 2016; 126(4):1198-207. PMC: 4811121. DOI: 10.1172/JCI81134. View

18.

Bouchareychas L, Duong P, Covarrubias S, Alsop E, Phu T, Chung A . Macrophage Exosomes Resolve Atherosclerosis by Regulating Hematopoiesis and Inflammation via MicroRNA Cargo. Cell Rep. 2020; 32(2):107881. PMC: 8143919. DOI: 10.1016/j.celrep.2020.107881. View

19.

Hergenreider E, Heydt S, Treguer K, Boettger T, Horrevoets A, Zeiher A . Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol. 2012; 14(3):249-56. DOI: 10.1038/ncb2441. View

20.

Zamani P, Fereydouni N, Butler A, Gholizadeh Navashenaq J, Sahebkar A . The therapeutic and diagnostic role of exosomes in cardiovascular diseases. Trends Cardiovasc Med. 2018; 29(6):313-323. DOI: 10.1016/j.tcm.2018.10.010. View