Extracellular Non-Coding RNAs in Cardiovascular Diseases
Abstract
:1. Introduction
2. Ex-ncRNAs
2.1. Extracellular Small ncRNAs
2.2. Extracellular LncRNAs
2.3. Extracellular CircRNAs
3. Ex-ncRNAs as Biomarkers in CVDs
3.1. Atherosclerosis
3.1.1. Extracellular Small ncRNAs
3.1.2. Extracellular LncRNAs
3.1.3. Extracellular CircRNAs
3.2. Ischemic Heart Disease
3.2.1. Extracellular Small ncRNAs
3.2.2. Extracellular LncRNAs
3.2.3. Extracellular CircRNAs
3.3. Hypertension
Extracellular Small ncRNAs
3.4. Heart Failure
3.4.1. Extracellular Small ncRNAs
3.4.2. Extracellular LncRNAs
Reference | Ex-ncRNA | Carriers | Expression (↑) (↓) | Type of CVDs | |
---|---|---|---|---|---|
Kasey et al. [33] | miR-223 | HDL | ↑ | - | Atherosclerosis |
Huang et al. [35] | miR-92a | - | ↑ | - | Atherosclerosis |
Tao et al. [37] | LncRNA SOX2-OT | - | ↑ | - | Atherosclerosis |
Vilades et al. [38] | hsa_circ_0001445 | - | - | ↓ | Atherosclerosis |
Corsten et al. [46] | miR-208b | - | ↑ | - | Acute myocardial infarction |
Li et al. [11] | tDR-1:32-His-GTG-1, tDR-37:72-Val-TAC-1, tDR-1:32-Pro-AGG-1-M4, etc. | - | ↑ | Cardiac ischemia/reperfusion | |
tDR-1:36-Glu-CTC-1, tDR-1:36-Glu-CTC-1-D5G, tDR-1:36-Asp-GTC-2-M2, etc. | - | ↓ | |||
Chen et al. [47] | LncRNA-NEAT1, miR-204 | EV | ↑ | ↓ | Acute ST-segment elevation myocardial infarction |
Hildebrandt et al. [48] | miR-370-3p, miR-409-3p | EV | ↑ | - | Coronary heart disease |
Chen et al. [50] | microRNA 3113-5P | - | ↑ | - | Cardiac ischemia/Reperfusion injury |
Zheng et al. [53] | lncRNA ENST00000556899.1, lncRNA ENST00000575985.1 | EV | ↑ | - | Acute myocardial infarction |
Kishore et al. [54] | circRNA MICRA, circRNA-284, hsa-circ-0098964 | - | ↑ | ↓ | Myocardial infarction, Ischemic heart disease, Hypertension |
Suzuki et al. [61] | miR-133a, miR-27a | - | - | ↓ | Hypertension |
Wang et al. [62] | miR-92a | - | ↑ | - | Hypertension |
He et al. [66] | miR-200a-3p | - | ↑ | - | Hypertension |
Janjusevic et al. [68] | lncRNA LIPCAR, miR-192, miR-134a, miR-194, miR-30d | EV | ↑ | ↓ | Heart failure |
Li et al. [69] | miR-30d | EV | - | ↓ | Heart failure |
Wu et al. [70] | miR-92b-5p | EV | ↑ | - | Heart failure |
4. Ex-ncRNAs as Therapeutic Targets in CVDs
4.1. Atherosclerosis
4.1.1. Extracellular Small ncRNA
4.1.2. Extracellular LncRNAs
4.1.3. Extracellular CircRNAs
4.2. Ischemic Heart Disease
4.2.1. Extracellular Small ncRNAs
4.2.2. Extracellular LncRNAs
4.2.3. Extracellular CircRNAs
4.3. Hypertension
Extracellular Small ncRNAs
4.4. Cardiac Hypertrophy
Extracellular Small ncRNAs
4.5. Heart Failure
4.5.1. Extracellular Small ncRNAs
4.5.2. Extracellular LncRNAs
Reference | Donor Cells | Ex-ncRNAs | Carriers | Expression Quantity (↑) (↓) | Target/Pathway | Type of CVDs | |
---|---|---|---|---|---|---|---|
Shimada et al. [82] | - | miR-146a-5p | EV | ↑ | - | TLR7 | Atherosclerosis |
Shan et al. [84] | Human umbilical vein endothelial cells | lncRNA-RNCR3 | EV | ↑ | - | miR-185-5p/KLF2 | Atherosclerosis |
Yang et al. [85] | - | hsa_circ_0001445 | - | - | ↓ | mir-208b-5p/ABCG1 | Atherosclerosis |
Liu et al. [89] | M1-like macrophage | miR-155 | EV | ↑ | - | Sirt1/AMPKα2 and RAC1-PAK2 | Acute myocardial infarction |
Long et al. [90] | M2-like macrophage | miR-1271-5p | EV | ↑ | - | SOX6 | Acute myocardial infarction |
Li et al. [69] | Cardiomyocytes | miR-30d | EV | ↑ | - | MAP4K4 and integrin α5 | Ischemic HF |
Liu et al. [91] | Dendritic cell | miR-494-3p | EV | ↑ | - | VEGF | Myocardial infarction |
Li et al. [92] | MSC | miR-486-5p | EV | ↑ | - | MMP 19/VEGF | Myocardial infarction |
Cheng et al. [93] | MSC | miR-210 | EV | ↑ | - | AIFM3/PI3K/AKT and p53 | Myocardial infarction |
Mao et al. [94] | MSC | miR-224-5p | EV | ↑ | - | TXNIP/GATA4/Bcl-2 | Ischemia-reperfusion injury |
He et al. [95] | MSC | miR-150-5p | EV | ↑ | - | TXNIP | Ischemia-reperfusion injury |
Li et al. [96] | BMSC | miR-29c | EV | ↑ | - | PTEN/Akt/mTOR | Ischemia-reperfusion injury |
Zou et al. [97] | - | miR-149, let-7c | EV | ↑ | - | miR-149/Let-7c/FASLG | Ischemia-reperfusion injury |
Fu et al. [98] | BMSC | miR-338 | EV | ↑ | - | MAP3K2/JNK axis | Myocardial infarction |
Walravens et al. [99,100,101,102] | CDC | miR-26a, miR-146a, miR-181b | EV | ↑ | - | Adam17, TLR-NFkB, PKCδ | Myocardial infarction |
Moghiman et al. [104] | MSC, Cardiomyocyte, EC | miR-23a-3p, miR-424, let-7f, miR-378, miR-214 | EV | ↑ | - | HOXA5, GAX, p38 MAPK, Smad2/3, ATM | Myocardial infarction |
Gou et al. [105] | Cardiomyocyte | miR-19a-3p | EV | ↑ | - | HIF-1α | Myocardial infarction |
Geng et al. [106] | Cardiomyocyte | miR-143 | EV | - | ↓ | IGF-IR/NO | Myocardial infarction |
Liao et al. [107] | CT | miR-21-5p | EV | ↑ | - | Cdip1/caspase-3 | Myocardial infarction |
Li et al. [108] | BMSC | lncRNA HCP5 | EV | ↑ | - | miR-497/IGF1/PI3K/AKT | Ischemia-reperfusion injury |
Diao et al. [109] | hUCMSC | lncRNA UCA1 | EV | ↑ | - | miR-143/Bcl-2/Beclin-1 | Ischemia-reperfusion injury |
Wang et al. [110] | Cardiomyocyte | circ-HIPK3 | EV | ↑ | - | miR-29a/VEGFA | Myocardial infarction |
Wang et al. [111] | M2-like macrophage | circRNA-UB3A | EV | ↑ | - | miR-138-5p/RhoC | Myocardial fibrosis after myocardial infarction |
Zhang et al. [112] | - | miR-483 | - | - | ↓ | TGF-β, TGFBR2, β-catenin, CTGF, IL-1β, ET-1 | Hypertension |
Shang et al. [113] | - | miR-483-3p | EV | ↑ | - | TGF-β, CTGF, ACE1, ET-1 | Hypertension |
Niu et al. [116] | - | miR-634 | - | - | ↓ | Wnt/β-catenin | Hypertension |
Xiang et al. [119] | Cardiomyocyte | miR-217 | EV | ↑ | - | PTEN | Cardiac hypertrophy |
Claudia et al. [120] | Cardiac fibroblast | miR-21-3p | EV | ↑ | - | SH3 domain-containing protein 2 and PDZ and LIM domain 5 | Cardiac hypertrophy |
Thum et al. [121] | - | miR-21 | - | ↑ | - | ERK-MAPK and Spry1 | Cardiac hypertrophy |
Yu et al. [125] | Macrophage | miR-155 | EV | ↑ | - | Son of Sevenless 1 and Suppressor of Cytokine Signaling 1 | Cardiac hypertrophy |
Yang et al. [129] | Telocyte | miR-30b | EV | ↑ | - | Runx2/Wnt/β-catenin | Cardiac hypertrophy |
Li et al. [130] | Cardiac stromal cell | miR-21-5p | EV | ↑ | - | phosphatase and tensin homolog/Akt | HF |
Li et al. [131,132,133] | - | lncExACT1 | - | ↑ | - | DCHS2 | HF |
5. Clinical Developments and Applications of Ex-ncRNAs in CVDs
5.1. Ex-ncRNAs as Biomarkers
5.2. Ex-ncRNAs as Therapeutics Targets
6. Conclusions and Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Stage | Drug | Modification and Delivery | Target Gene | Disease | Comments |
---|---|---|---|---|---|
Clinical trials | AZD8601 | naked mRNA | VEGF-A | HF | Phase 2 |
CDR132L | ASO | miR-321 | HF | Phase 2 | |
IONIS-AGT-LRx | Antisense | Angiotensinogen | HF | Phase 2 | |
Olezarsen | Antisense | ApoC-III | Lipid disorders | Phase 3 | |
Olpasiran | siRNA | Lp(a) | Lipid disorders | Phase 2 | |
Pelacarsen | Antisense | Lp(a) | Lipid disorders | Phase 3 | |
Vupanorsen | Antisense | ANGPTL3 | Lipid disorders | Phase 2 | |
FDA/EMA approved | Inclisiran | siRNA | PCSK9 | Lipid disorders | FDA approved |
Volanesorsen | ASO | APO-C3 | Triglycerides | EMA approved |
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Jiapaer, Z.; Li, C.; Yang, X.; Sun, L.; Chatterjee, E.; Zhang, L.; Lei, J.; Li, G. Extracellular Non-Coding RNAs in Cardiovascular Diseases. Pharmaceutics 2023, 15, 155. https://doi.org/10.3390/pharmaceutics15010155
Jiapaer Z, Li C, Yang X, Sun L, Chatterjee E, Zhang L, Lei J, Li G. Extracellular Non-Coding RNAs in Cardiovascular Diseases. Pharmaceutics. 2023; 15(1):155. https://doi.org/10.3390/pharmaceutics15010155
Chicago/Turabian StyleJiapaer, Zeyidan, Chengyu Li, Xinyu Yang, Lingfei Sun, Emeli Chatterjee, Lingying Zhang, Ji Lei, and Guoping Li. 2023. "Extracellular Non-Coding RNAs in Cardiovascular Diseases" Pharmaceutics 15, no. 1: 155. https://doi.org/10.3390/pharmaceutics15010155