Extracellular Vesicles in Cardiovascular Diseases: Alternative Biomarker Sources, Therapeutic Agents, and Drug Delivery Carriers
Abstract
:1. Introduction
2. Extracellular Vesicles: Origin, Types, and Characterizations
3. Extracellular Vesicle Contents in CVD
3.1. Extracellular Vesicle MicroRNA
3.2. Extracellular Vesicle Proteins
3.3. Extracellular Vesicle Lipids
4. Intrinsic Activity of EVs: Potential Therapeutic Agents in CVD
4.1. Extracellular Vesicles Derived from Stem Cells
4.2. Extracellular Vesicles Derived from Cardiomyocytes and Cardiac Progenitor Cells
4.3. Extracellular Vesicles Derived from Other Cell Types
5. Extracellular Vesicles as a Potential Drug Delivery System in CVD
5.1. Atherosclerosis
5.2. Myocardial Infarction
5.3. Stroke
6. Extracellular Vesicles as a Theranostic Platform
7. Limitations and Future Perspective
Author Contributions
Funding
Conflicts of Interest
Abbreviations
2D-DIGE | two-dimensional difference gel electrophoresis |
ACS | acute coronary syndrome |
ATG7 | autophagy related 7 |
BBB | blood–brain barrier |
CABG | coronary artery bypass graft |
CHP | cardiac homing peptide |
CTP | cardiac targeting peptide |
CVD | cardiovascular disease |
DDS | drug delivery system |
DLS | dynamic light scattering |
DNA | deoxyribonucleic acid |
EMPRINN | extracellular matrix metalloproteinase inducer |
EPR | enhanced permeability and retention |
ESCRT | endosomal sorting complex required for transport |
EVs | extracellular vesicles |
FACS | fluorescence-activated cell sorting |
FDA | food drug administration |
GC | gas chromatography |
HF | heart failure |
HSP20 | heat shock protein 20 |
HSP60 | heat shock protein 60 |
IONPs | iron-oxide nanoparticles |
iPS | induced pluripotent stem cells |
IR | ischemic reperfusion |
ISEV | international society of extracellular vesicles |
KO | knock-out |
LC | liquid chromatography |
lncRNA | long-non-coding RNA |
MALDI-TOF | matrix-assisted laser desorption/ionization-time of flight |
MI | myocardial infarction |
miRNA | microRNA |
MMPs | matrix metalloproteinases |
mRNA | messenger RNA |
MS | mass spectrometry |
MSC | mesenchymal stem cells |
NF-κB | nuclear factor kappa-light-chain-enhancer of activated B cells |
NIHSS | national institutes of health stroke scale |
NTA | nanoparticle tracking analysis |
ORF | open reading frame |
PE | phosphatidylethanolamine |
pIgR | polygenic immunoglobulin receptor |
PS | phosphatidylserine |
RISC | RNA-induced silencing complex |
RNA | ribonucleic acid |
RT-qPCR | reverse transcription quantitative polymerase chain reaction |
siRNA | small interfering RNA |
SPIOs | superparamagnetic iron-oxide nanoparticles |
STEMI | st-elevation myocardial infarction |
TEM | transmission electron microscopy |
TLR4 | toll-like receptor 4 |
TNF-α | tumor necrosis factor-alpha |
tRNA | transfer RNA |
TSG101 | tumor susceptibility gene 101 |
VEGF | vascular endothelial growth factor |
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Disease | Sample Size | Source | Methods of Isolation | EVs Characterized | Screening Method | Quantification Method | Analytes Measured | Significant Candidates | Potential Application | Ref. |
---|---|---|---|---|---|---|---|---|---|---|
Acute Ischemic Stroke | 50 | Serum | Precipitation | TEM; Western blot | Based on previous reports | RT-qPCR | miR-134 | miR-134 | Diagnosis and prognosis | [59] |
Acute Ischemic Stroke | 50 | Serum | Precipitation | TEM; Western blot | Based on previous reports | RT-qPCR | miR-223 | miR-223 | Diagnosis and prognosis | [60] |
Heart Failure | 31 | Plasma | Precipitation | Not available | Based on previous reports | RT-qPCR | miR-221, miR-15a, miR-122, miR-21, miR-29, miR-30d, miR-133a, miR-425, miR-744 | miR-21, miR-425, miR-744 | Diagnosis, prognosis and therapeutic candidates | [62] |
Acute Heart Failure | 28 | Serum | Precipitation | TEM; Western blot; DLS | Based on previous reports | RT-qPCR | miR-92b-5p, miR-192-5p, miR-320a | miR-92b-5p | Diagnosis | [63] |
Acute Myocardial Infarction | 21 | Serum | Precipitation | Western blot | miRNA profiling through TaqMan Human MicroRNA Array | RT-qPCR; | 377 miRNAs | miR-192, miR-194, miR-34a | Prognosis | [64] |
Atrial fibrillation | 40 | Serum | Precipitation | TEM; NTA; Western blot | miRNA microarray | RT-qPCR | miR-107, miR-320d, miR-103a, miR-486, miR-let-7b | miR-107, miR-320d, miR-103a, miR-486, miR-let-7b | Diagnosis, prognosis | [57] |
Hyper-tension | 22 | Serum | Ultra-centrifugation | TEM; Immune-gold labelling | Nanostring nCounter® platform | Nanostring nCounter® platform | 800 miRNAs | miR-199a/b, miR-223–3p | Early diagnosis | [67] |
Obesity | 883 | Plasma | Ultra-centrifugation | TEM; FACS; NTA | miRNA screening through QuantStudio™12 K FlexOpenArray® Platform | miRNA screening through QuantStudio™12 K FlexOpenArray® Platform | 754 miRNAs | miR-let-7c-5p, miR-106a-5p, miR-143-3p; miR-185-5p, miR-218-5p; miR-331-3p, miR-642-5p, miR-652-3p, miR-99b-5p | Early diagnosis | [68] |
Coronary Artery Disease | 21 | Plasma | Column-based system (Exo-spin Mini Columns) | NTA; TEM; Western blot | Based on previous reports | RT-qPCR | 14 miRNAs | miR-1, miR-24, miR-133a, miR-133b, miR-210 | Diagnosis | [73] |
Acute Coronary Syndrome | 475 | Serum | Precipitation | TEM; FACS; NTA; Western blot | Differential quantitative proteomics and ingenuity pathway analysis | Multiplex immunoassay | polygenic immunoglobulin receptor (pIgR), cystatin C, and complement factor C5a | pIgR, cystatin C | Diagnosis | [40] |
Acute Myocardial Infarction | 25 | Plasma | Ultra-centrifugation | FACS; TEM; DLS | 2D-DIGE; LC-MS/MS; MALDI-TOF coupled with ingenuity pathway analysis | 2D-DIGE; Western blot | 25 ORFs derived from 102 differentially regulated proteins spot identified through 2D-DIGE | A2-macroglobulin isoforms, Fibrinogen, Viperin | Diagnosis and therapeutic targets | [80] |
Vascular Disease | 1060 | Plasma | Precipitation | TEM; FACS; NTA; Western blot | Differential quantitative proteomics and ingenuity pathway analysis | Multiplex immunoassay | Cystatin C, Serpin G1, Serpin F2, and CD14 | Cystatin C, Serpin F2, and CD14 | Prognosis | [41] |
Dyspnea and Heart Failure | 404 | Plasma | Sequential density precipitation | TEM; Western blot | Based on previous study | Multiplex immunoassay | Cystatin C, Serpin G1, Serpin F2, and CD14 | CD14, SerpinG1, and SerpinF2 | Prognosis | [42] |
Vascular Disease and Obesity | 1060 | Plasma | Precipitation | TEM; FACS; NTA; Western blot | Differential quantitative proteomics and ingenuity pathway analysis | Multiplex immunoassay | Cystatin C, Serpin G1, Serpin F2, and CD14 | Cystatin C, CD14 | Prognosis and therapeutic target | [81] |
Obesity | 22 | Plasma | Ultra-centrifugation | TEM; FACS; NTA; Western blot | 2D-DIGE-based proteomic approach | 2D-Western blot | Entire Proteome | C3, C4, Fibrinogen, Adiponectin | Early diagnosis | [82] |
Therapeutics Encapsulated | In vivo Model | Outcome | Ref. |
---|---|---|---|
Simvastatin/Alendronate | Carotid-injured rat model | Suppressed neointimal formation | [171,172] |
Nitric oxide | Carotid-injured rabbit model | Suppressed neointimal formation | [173] |
Berberine | Myocardial infarction murine model | Improvement of cardiac function | [152] |
VEGF | Myocardial infarction rat model | Improved cardiac functions | [174] |
Cyclopentenone prostaglandin | Hyperlipemic diet atherosclerotic murine model | Vascular injuries recovery | [175] |
Fumagillin | Hyperlipemic diet atherosclerotic murine model | Reduced atherosclerotic lesions | [176] |
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Chong, S.Y.; Lee, C.K.; Huang, C.; Ou, Y.H.; Charles, C.J.; Richards, A.M.; Neupane, Y.R.; Pavon, M.V.; Zharkova, O.; Pastorin, G.; et al. Extracellular Vesicles in Cardiovascular Diseases: Alternative Biomarker Sources, Therapeutic Agents, and Drug Delivery Carriers. Int. J. Mol. Sci. 2019, 20, 3272. https://doi.org/10.3390/ijms20133272
Chong SY, Lee CK, Huang C, Ou YH, Charles CJ, Richards AM, Neupane YR, Pavon MV, Zharkova O, Pastorin G, et al. Extracellular Vesicles in Cardiovascular Diseases: Alternative Biomarker Sources, Therapeutic Agents, and Drug Delivery Carriers. International Journal of Molecular Sciences. 2019; 20(13):3272. https://doi.org/10.3390/ijms20133272
Chicago/Turabian StyleChong, Suet Yen, Choon Keong Lee, Chenyuan Huang, Yi Hsuan Ou, Christopher J. Charles, Arthur Mark Richards, Yub Raj Neupane, Maria Vazquez Pavon, Olga Zharkova, Giorgia Pastorin, and et al. 2019. "Extracellular Vesicles in Cardiovascular Diseases: Alternative Biomarker Sources, Therapeutic Agents, and Drug Delivery Carriers" International Journal of Molecular Sciences 20, no. 13: 3272. https://doi.org/10.3390/ijms20133272