# Extracellular Vesicles as Biomarkers and Non-Surgical Therapeutics in Cardiovascular Diseases

**Authors:** Dana A. Almazroua, Kelsey C. Muir, M. Ruhul Abid

PMC · DOI: 10.3390/jcm15041537 · 2026-02-15

## TL;DR

Extracellular vesicles (EVs) could serve as non-invasive biomarkers and therapeutics for cardiovascular diseases, but more research is needed to validate their clinical use.

## Contribution

The paper reviews the potential of EVs in cardiovascular disease diagnostics and therapy, highlighting current evidence and remaining challenges.

## Key findings

- EVs transfer bioactive molecules that influence disease progression and cardiac repair.
- EVs show promise as biomarkers and cell-free therapeutics for conditions like myocardial infarction and heart failure.
- Major challenges include inconsistent methodologies and limited clinical translation of EV-based approaches.

## Abstract

Background: Cardiovascular disease (CVD), including myocardial ischemia, remains the leading cause of mortality. Current therapies for ischemic myocardium rely largely on invasive revascularization strategies, highlighting the need for improved non-invasive diagnostic and therapeutic approaches. Recent studies suggest that extracellular vesicles (EVs) play a critical role in cardiovascular pathophysiology and may offer novel clinical applications. Methods: This review synthesizes current preclinical and clinical literature on EV biology, including their classification, isolation, and characterization methods, and mechanisms of Intercellular communication. Published studies evaluating EVs as biomarkers and non-surgical therapeutics across major cardiovascular conditions were critically analyzed. Results: EVs facilitate intercellular communication by transferring bioactive molecules that influence disease progression and cardiac repair. Accumulating evidence supports their potential utility as biomarkers for disease prediction and severity assessment, as well as cell-free therapeutics in myocardial infarction, cardiomyopathies, atrial fibrillation, and heart failure. However, significant gaps remain, including the lack of validated EV-based biomarkers, inconsistent isolation and characterization methodologies, limited in vivo tracking data, and barriers to clinical translation. Conclusions: EVs represent a promising frontier in non-invasive cardiovascular diagnostics and therapeutics. Addressing current methodological and translational challenges, alongside advances in EV bioengineering, will be essential to realize their full clinical potential in CVD management.

## Linked entities

- **Diseases:** cardiovascular disease (MONDO:0004995), myocardial ischemia (MONDO:0024644), myocardial infarction (MONDO:0005068), cardiomyopathies (MONDO:0004994), atrial fibrillation (MONDO:0004981), heart failure (MONDO:0005252)

## Full-text entities

- **Genes:** MIR181A1 (microRNA 181a-1) [NCBI Gene 406995] {aka MIR213, MIRN181A1, MIRN213, hsa-mir-181a-1, mir-181a-1, mir-213}, MIR2110 (microRNA 2110) [NCBI Gene 100302224] {aka hsa-mir-2110, mir-2110}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, PDCD6IP (programmed cell death 6 interacting protein) [NCBI Gene 10015] {aka AIP1, ALIX, DRIP4, HP95, MCPH29}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, Hif1a (hypoxia inducible factor 1, alpha subunit) [NCBI Gene 15251] {aka HIF-1-alpha, HIF1-alpha, HIF1alpha, MOP1, bHLHe78}, HSPD1 (heat shock protein family D (Hsp60) member 1) [NCBI Gene 3329] {aka CPN60, GROEL, HLD4, HSP-60, HSP60, HSP65}, ITGB1 (integrin subunit beta 1) [NCBI Gene 3688] {aka CD29, FNRB, GPIIA, MDF2, MSK12, VLA-BETA}, CD81 (CD81 molecule) [NCBI Gene 975] {aka CVID6, S5.7, TAPA1, TSPAN28}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, CST3 (cystatin C) [NCBI Gene 1471] {aka ADLDWA, ARMD11, HEL-S-2}, MIR1225 (microRNA 1225) [NCBI Gene 100188847] {aka MIRN1225}, HSPA8 (heat shock protein family A (Hsp70) member 8) [NCBI Gene 3312] {aka HEL-33, HEL-S-72p, HSC54, HSC70, HSC71, HSP71}, MIR34A (microRNA 34a) [NCBI Gene 407040] {aka MIRN34A, miRNA34A, mir-34, mir-34a}, KLF2 (KLF transcription factor 2) [NCBI Gene 10365] {aka LKLF}, TSG101 (tumor susceptibility 101) [NCBI Gene 7251] {aka TSG10, VPS23}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, MIR3180-3 (microRNA 3180-3) [NCBI Gene 100422836], SERPINA1 (serpin family A member 1) [NCBI Gene 5265] {aka A1A, A1AT, AAT, PI, PI1, PRO2275}, CD14 (CD14 molecule) [NCBI Gene 929], Zeb1 (zinc finger E-box binding homeobox 1) [NCBI Gene 21417] {aka 3110032K11Rik, AREB6, BZP, MEB1, Nil2, TCF-8}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CD9 (CD9 molecule) [NCBI Gene 928] {aka BTCC-1, DRAP-27, MIC3, MRP-1, TSPAN-29, TSPAN29}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, Nox4 (NADPH oxidase 4) [NCBI Gene 50490], AGO2 (argonaute RISC catalytic component 2) [NCBI Gene 27161] {aka CASC7, EIF2C2, LESKRES, LINC00980, PPD, Q10}, CDH2 (cadherin 2) [NCBI Gene 1000] {aka ACOGS, ADHD8, ARVD14, CD325, CDHN, CDw325}, USP14 (ubiquitin specific peptidase 14) [NCBI Gene 9097] {aka TGT, Ubp6}, SMAD2 (SMAD family member 2) [NCBI Gene 4087] {aka CHTD8, JV18, JV18-1, LDS6, MADH2, MADR2}, MIR107 (microRNA 107) [NCBI Gene 406901] {aka MIRN107, miR-107}, MIR95 (microRNA 95) [NCBI Gene 407052] {aka MIRN95, hsa-mir-95, miR-95}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Bax (BCL2-associated X protein) [NCBI Gene 12028], IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, TF (transferrin) [NCBI Gene 7018] {aka HEL-S-71p, PRO1557, PRO2086, TFQTL1}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, CD63 (CD63 molecule) [NCBI Gene 967] {aka AD1, HOP-26, ME491, MLA1, OMA81H, Pltgp40}, SLC3A2 (solute carrier family 3 member 2) [NCBI Gene 6520] {aka 4F2, 4F2HC, 4T2HC, CD98, CD98HC, MDU1}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, PTK2 (protein tyrosine kinase 2) [NCBI Gene 5747] {aka FADK, FADK 1, FAK, FAK1, FRNK, PPP1R71}, BSG (basigin (Ok blood group)) [NCBI Gene 682] {aka 5F7, CD147, EMMPRIN, EMPRIN, HAb18G, OK}, PVT1 (Pvt1 oncogene) [NCBI Gene 5820] {aka LINC00079, MIR1204HG, NCRNA00079, TP53LC09, onco-lncRNA-100}, CCR2 (C-C motif chemokine receptor 2) [NCBI Gene 729230] {aka CC-CKR-2, CCR-2, CCR2A, CCR2B, CD192, CKR2}, Tsc22d1 (TSC22 domain family, member 1) [NCBI Gene 21807] {aka Egr5, Gm19597, TSC-22, Tgfb1i4, Tsc, Tsc22}, MIR223 (microRNA 223) [NCBI Gene 407008] {aka MIRN223, miRNA223, mir-223}, ACSM3 (acyl-CoA synthetase medium chain family member 3) [NCBI Gene 6296] {aka SA, SAH}, SLC7A11 (solute carrier family 7 member 11) [NCBI Gene 23657] {aka CCBR1, xCT}, HSP90AB1 (heat shock protein 90 alpha family class B member 1) [NCBI Gene 3326] {aka D6S182, HSP84, HSP90B, HSPC2, HSPCB}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, CCND3 (cyclin D3) [NCBI Gene 896], CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, ATP1A1 (ATPase Na+/K+ transporting subunit alpha 1) [NCBI Gene 476] {aka CMT2DD, HOMGSMR2}, CD82 (CD82 molecule) [NCBI Gene 3732] {aka 4F9, C33, GR15, IA4, KAI1, R2}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}
- **Diseases:** vascular dysfunction (MESH:D002561), EV (MESH:C535509), lung injury (MESH:D055370), impaired ventricular filling (MESH:D018754), insulin resistance (MESH:D007333), MI (MESH:D009203), DCM (MESH:D002311), CVD (MESH:D002318), hypertrophy (MESH:D006984), reduced cardiac output (MESH:D002303), DM (MESH:D003920), rupture (MESH:D012421), IHD (MESH:D017202), ischemic myocardium (MESH:D017682), ischemic (MESH:D002545), AF (MESH:D001281), calcification (MESH:D002114), HTN (MESH:D006973), Tumorigenicity (MESH:D002471), hyperglycemic (MESH:D006944), left ventricular hypertrophy (MESH:D017379), Diabetic Cardiomyopathy (MESH:D058065), death (MESH:D003643), coronary microvascular dysfunction (MESH:D003327), atherosclerosis (MESH:D050197), injury to (MESH:D014947), pericarditis (MESH:D010493), cardiac inflammation (MESH:D007249), atrial fibrosis (MESH:D005355), metabolic syndrome (MESH:D024821), ischemia/reperfusion (I/R) injury (MESH:D015427), thrombosis (MESH:D013927), iron deficiency (MESH:D000090463), Hypoxia (MESH:D000860), cardiotoxicity (MESH:D066126), genetic disorder (MESH:D030342), Cardiomyopathies (MESH:D009202), ventricles (MESH:D002551), HCM (MESH:D002312), CAD (MESH:D003324), stroke (MESH:D020521), cardiac diseases (MESH:D006331), sudden cardiac death (MESH:D016757), myocardial steatosis (MESH:D005234), diastolic dysfunction (MESH:D018487), infarct (MESH:D007238), CHF (MESH:D006333), arrhythmias (MESH:D001145), hypoxic (MESH:D002534), renal dysfunction (MESH:D007674)
- **Chemicals:** phosphatidylserine (MESH:D010718), fatty acid (MESH:D005227), sulfhydryl (MESH:D013438), ginsenoside RG1 (MESH:C035054), DOX (MESH:D004317), acids (MESH:D000143), oxygen (MESH:D010100), Ang-II (-), curcumin (MESH:D003474), glucose (MESH:D005947), cholesterol (MESH:D002784), ceramide (MESH:D002518), calcium (MESH:D002118), glycolipids (MESH:D006017), warfarin (MESH:D014859), ICG-001 (MESH:C492448), lipid (MESH:D008055), sucrose (MESH:D013395), iron (MESH:D007501), aspirin (MESH:D001241), maleimide (MESH:C043592), phospholipids (MESH:D010743), 2,4-dinitrophenol (MESH:D019297), rivaroxaban (MESH:D000069552)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12941460/full.md

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Source: https://tomesphere.com/paper/PMC12941460