An Integrative Study of Aortic mRNA/miRNA Longitudinal Changes in Long-Term LVAD Support
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Subjects
4.2. Sampling
4.3. mRNA and miRNA Analysis
4.4. Processing of mRNA Sequencing Data
4.5. DESeq2 Analysis of mRNA Expression
4.6. Gene Ontology Analysis
4.7. miRNA Profile Analysis
4.8. Integrated mRNA/miRNA Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Saito, T.; Wassilew, K.; Gorodetski, B.; Stein, J.; Falk, V.; Krabatsch, T.; Potapov, E. Aortic Valve Pathology in Patients Supported by Continuous-Flow Left Ventricular Assist Device. Circ. J. 2016, 80, 1371–1377. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Segura, A.M.; Gregoric, I.; Radovancevic, R.; Demirozu, Z.T.; Buja, L.M.; Frazier, O.H. Morphologic changes in the aortic wall media after support with a continuous-flow left ventricular assist device. J. Heart Lung Transplant. 2013, 32, 1096–1100. [Google Scholar] [CrossRef]
- Patel, A.C.; Dodson, R.B.; Cornwell, W.K., 3rd; Hunter, K.S.; Cleveland, J.C., Jr.; Brieke, A.; Lindenfeld, J.; Ambardekar, A.V. Dynamic Changes in Aortic Vascular Stiffness in Patients Bridged to Transplant With Continuous-Flow Left Ventricular Assist Devices. JACC Heart Fail. 2017, 5, 449–459. [Google Scholar] [CrossRef]
- Fine, N.M.; Park, S.J.; Stulak, J.M.; Topilsky, Y.; Daly, R.C.; Joyce, L.D.; Pereira, N.L.; Schirger, J.A.; Edwards, B.S.; Lin, G.; et al. Proximal thoracic aorta dimensions after continuous-flow left ventricular assist device implantation: Longitudinal changes and relation to aortic valve insufficiency. J. Heart Lung Transplant. 2016, 35, 423–432. [Google Scholar] [CrossRef]
- Bartel, D.P. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004, 116, 281–297. [Google Scholar] [CrossRef] [Green Version]
- Thum, T. Facts and updates about cardiovascular non-coding RNAs in heart failure. ESC Heart Fail. 2015, 2, 108–111. [Google Scholar] [CrossRef] [PubMed]
- Kumar, S.; Williams, D.; Sur, S.; Wang, J.Y.; Jo, H. Role of flow-sensitive microRNAs and long noncoding RNAs in vascular dysfunction and atherosclerosis. Vasc. Pharm. 2019, 114, 76–92. [Google Scholar] [CrossRef]
- Archacki, S.; Wang, Q. Expression profiling of cardiovascular disease. Hum. Genom. 2004, 1, 355–370. [Google Scholar] [CrossRef] [Green Version]
- Corley, S.M.; Troy, N.M.; Bosco, A.; Wilkins, M.R. QuantSeq. 3′ Sequencing combined with Salmon provides a fast, reliable approach for high throughput RNA expression analysis. Sci. Rep. 2019, 9, 18895. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Junyan, X.; Guo-Ping, S. Vascular wall extracellular matrix proteins and vascular diseases. Mol. Basis Dis. 2014, 1842, 2106–2119. [Google Scholar] [CrossRef] [Green Version]
- Coffey, S.; Williams, M.J.; Phillips, L.V.; Galvin, I.F.; Bunton, R.W.; Jones, G.T. Integrated microRNA and messenger RNA analysis in aortic stenosis. Sci. Rep. 2016, 6, 36904. [Google Scholar] [CrossRef] [Green Version]
- Ambardekar, A.V.; Hunter, K.S.; Babu, A.N.; Tuder, R.M.; Dodson, R.B.; Lindenfeld, J. Changes in Aortic Wall Structure, Composition, and Stiffness With Continuous-Flow Left Ventricular Assist Devices: A Pilot Study. Circ. Heart Fail. 2015, 8, 944–952. [Google Scholar] [CrossRef]
- Wang, X.; LeMaire, S.A.; Chen, L.; Shen, Y.H.; Gan, Y.; Bartsch, H.; Carter, S.A.; Utama, B.; Ou, H.; Coselli, J.S.; et al. Increased collagen deposition and elevated expression of connective tissue growth factor in human thoracic aortic dissection. Circulation 2006, 114, I200–I205. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- D’Ambrosi, N.; Milani, M.; Apolloni, S. S100A4 in the Physiology and Pathology of the Central and Peripheral Nervous System. Cells 2021, 10, 798. [Google Scholar] [CrossRef]
- Li, Z.; Li, Y.; Liu, S.; Qin, Z. Extracellular S100A4 as a key player in fibrotic diseases. J. Cell. Mol. Med. 2020, 24, 5973–5983. [Google Scholar] [CrossRef] [Green Version]
- Kostopoulos, C.G.; Spiroglou, S.G.; Varakis, J.N.; Apostolakis, E.; Papadaki, H.H. Chemerin and CMKLR1 expression in human arteries and periadventitial fat: A possible role for local chemerin in atherosclerosis? BMC Cardiovasc. Disord. 2014, 14, 56. [Google Scholar] [CrossRef]
- Patel, C.B.; Cowger, J.A.; Zuckermann, A. A contemporary review of mechanical circulatory support. J. Heart Lung Transplant. 2014, 33, 667–674. [Google Scholar] [CrossRef] [PubMed]
- Holtz, J.; Teuteberg, J. Management of aortic insufficiency in the continuous flow left ventricular assist device population. Curr. Heart Fail. Rep. 2014, 11, 103–110. [Google Scholar] [CrossRef]
- Imamura, T.; Kim, G.; Nitta, D.; Fujino, T.; Smith, B.; Kalantari, S.; Nguyen, A.; Narang, N.; Holzhauser, L.; Grinstein, J.; et al. Aortic Insufficiency and Hemocompatibility-related Adverse Events in Patients with Left Ventricular Assist Devices. J. Card. Fail. 2019, 25, 787–794. [Google Scholar] [CrossRef]
- Yu, C.K.; Xu, T.; Assoian, R.K.; Rader, D.J. Mining the Stiffness-Sensitive Transcriptome in Human Vascular Smooth Muscle Cells Identifies Long Noncoding RNA Stiffness Regulators. Arterioscler. Thromb. Vasc. Biol. 2018, 38, 164–173. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Demirozu, Z.T.; Radovancevic, R.; Hochman, L.F.; Gregoric, I.D.; Letsou, G.V.; Kar, B.; Bogaev, R.C.; Frazier, O.H. Arteriovenous malformation and gastrointestinal bleeding in patients with the HeartMate II left ventricular assist device. J. Heart Lung Transplant. 2011, 30, 849–853. [Google Scholar] [CrossRef] [PubMed]
- Uriel, N.; Pak, S.W.; Jorde, U.P.; Jude, B.; Susen, S.; Vincentelli, A.; Ennezat, P.V.; Cappleman, S.; Naka, Y.; Mancini, D. Acquired von Willebrand syndrome after continuous-flow mechanical device support contributes to a high prevalence of bleeding during long-term support and at the time of transplantation. J. Am. Coll. Cardiol. 2010, 56, 1207–1213. [Google Scholar] [CrossRef] [Green Version]
- Kato, T.S.; Schulze, P.C.; Yang, J.; Chan, E.; Shahzad, K.; Takayama, H.; Uriel, N.; Jorde, U.; Farr, M.; Naka, Y.; et al. Pre-operative and post-operative risk factors associated with neurologic complications in patients with advanced heart failure supported by a left ventricular assist device. J. Heart Lung Transplant. 2012, 31, 1–8. [Google Scholar] [CrossRef] [Green Version]
- Trachtenberg, B.H.; Cordero-Reyes, A.M.; Aldeiri, M.; Alvarez, P.; Bhimaraj, A.; Ashrith, G.; Elias, B.; Suarez, E.E.; Bruckner, B.; Loebe, M.; et al. Persistent blood stream infection in patients supported with a continuous-flow left ventricular assist device is associated with an increased risk of cerebrovascular accidents. J. Card. Fail. 2015, 21, 119–125. [Google Scholar] [CrossRef]
- Najjar, S.S.; Slaughter, M.S.; Pagani, F.D.; Starling, R.C.; McGee, E.C.; Eckman, P.; Tatooles, A.J.; Moazami, N.; Kormos, R.L.; Hathaway, D.R.; et al. HVAD Bridge to Transplant ADVANCE Trial Investigators. An analysis of pump thrombus events in patients in the HeartWare ADVANCE bridge to transplant and continued access protocol trial. J. Heart Lung Transplant. 2014, 33, 23–34. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Starling, R.C.; Moazami, N.; Silvestry, S.C.; Ewald, G.; Rogers, J.G.; Milano, C.A.; Rame, J.E.; Acker, M.A.; Blackstone, E.H.; Ehrlinger, J.; et al. Unexpected abrupt increase in left ventricular assist device thrombosis. N. Engl. J. Med. 2014, 370, 33–40. [Google Scholar] [CrossRef] [Green Version]
- Cowger, J.; Pagani, F.D.; Haft, J.W.; Romano, M.A.; Aaronson, K.D.; Kolias, T.J. The development of aortic insufficiency in left ventricular assist device-supported patients. Circ. Heart Fail. 2010, 3, 668–674. [Google Scholar] [CrossRef] [Green Version]
- Pak, S.W.; Uriel, N.; Takayama, H.; Cappleman, S.; Song, R.; Colombo, P.C.; Charles, S.; Mancini, D.; Gillam, L.; Naka, Y.; et al. Prevalence of de novo aortic insufficiency during long-term support with left ventricular assist devices. J. Heart Lung Transplant. 2010, 29, 1172–1176. [Google Scholar] [CrossRef]
- Ivak, P.; Netuka, I.; Tucanova, Z.; Wohlfahrt, P.; Konarik, M.; Szarszoi, O.; Novakova, S.; Kubanek, M.; Lanska, V.; Pitha, J. The Effect of Artificial Pulsatility on the Peripheral Vasculature in Patients with a Continuous-Flow Ventricular Assist Device. Can. J. Cardiol. 2021. [Google Scholar] [CrossRef] [PubMed]
- Leeper, N.J.; Maegdefessel, L. Non-coding RNAs: Key regulators of smooth muscle cell fate in vascular disease. Cardiovasc. Res. 2018, 114, 611–621. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Morgan, N.; Warner, P.; Kiernan, M.; Al-Quthami, A.; Rahban, Y.; Pham, D.T.; DeNofrio, D.; Karas, R.; Kuvin, J. Arterial Stiffness and Vascular Endothelial Function in Patients with Long-Term Continuous-Flow Left Ventricular Assist Devices. J. Card. Fail. 2013, 19, S18. [Google Scholar] [CrossRef]
- Fernández-Hernando, C.; Suárez, Y. MicroRNAs in endothelial cell homeostasis and vascular disease. Curr. Opin. Hematol. 2018, 25, 227–236. [Google Scholar] [CrossRef]
- Kriegel, A.J.; Baker, M.A.; Liu, Y.; Liu, P.; Cowley, A.W., Jr.; Liang, M. Endogenous microRNAs in human microvascular endothelial cells regulate mRNAs encoded by hypertension-related genes. Hypertension 2015, 66, 793–799. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sun, X.; Sit, A.; Feinberg, M.W. Role of miR-181 family in regulating vascular inflammation and immunity. Trends Cardiovasc. Med. 2014, 24, 105–112. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lin, Z.; Ge, J.; Wang, Z.; Ren, J.; Wang, X.; Xiong, H.; Gao, J.; Zhang, Y.; Zhang, Q. Let-7e modulates the inflammatory response in vascular endothelial cells through ceRNA crosstalk. Sci. Rep. 2017, 7, 42498:1–42498:12. [Google Scholar] [CrossRef]
- Pin, A.L.; Houle, F.; Guillonneau, M.; Paquet, E.R.; Simard, M.J.; Huot, J. miR-20a represses endothelial cell migration by targeting MKK3 and inhibiting p38 MAP kinase activation in response to VEGF. Angiogenesis 2012, 15, 593–608. [Google Scholar] [CrossRef]
- Chamorro-Jorganes, A.; Araldi, E.; Rotllan, N.; Cirera-Salinas, D.; Suárez, Y. Autoregulation of glypican-1 by intronic microRNA-149 fine tunes the angiogenic response to FGF2 in human endothelial cells. J. Cell Sci. 2014, 127, 1169–1178. [Google Scholar] [CrossRef] [Green Version]
- Grundmann, S.; Hans, F.P.; Kinniry, S.; Heinke, J.; Helbing, T.; Bluhm, F.; Sluijter, J.P.; Hoefer, I.; Pasterkamp, G.; Bode, C.; et al. MicroRNA-100 regulates neovascularization by suppression of mammalian target of rapamycin in endothelial and vascular smooth muscle cells. Circulation 2011, 123, 999–1009. [Google Scholar] [CrossRef] [Green Version]
- Kane, N.M.; Howard, L.; Descamps, B.; Meloni, M.; McClure, J.; Lu, R.; McCahill, A.; Breen, C.; Mackenzie, R.M.; Delles, C.; et al. Role of MicroRNAs 99b, 181a, and 181b in the Differentiation of Human Embryonic Stem Cells to Vascular Endothelial Cells. Stem Cells 2012, 30, 643–654. [Google Scholar] [CrossRef] [Green Version]
- Tang, X.; Yin, R.; Shi, H.; Wang, X.; Shen, D.; Wang, X.; Pan, C. LncRNA ZFAS1 confers inflammatory responses and reduces cholesterol efflux in atherosclerosis through regulating miR-654-3p-ADAM10/RAB22A axis. Int. J. Cardiol. 2020, 315, 72–80. [Google Scholar] [CrossRef]
- Chen, C.; Ponnusamy, M.; Liu, C.; Gao, J.; Wang, K.; Li, P. MicroRNA as a Therapeutic Target in Cardiac Remodeling. Biomed. Res. Int. 2017, 2017, 1278436. [Google Scholar] [CrossRef] [Green Version]
- Henn, D.; Abu-Halima, M.; Wermke, D.; Falkner, F.; Thomas, B.; Köpple, C.; Ludwig, N.; Schulte, M.; Brockmann, M.A.; Kim, Y.J. MicroRNA-regulated pathways of flow-stimulated angiogenesis and vascular remodeling in vivo. J. Transl. Med. 2019, 17, 22. [Google Scholar] [CrossRef] [PubMed]
- Feng, J.; Zeng, C.; Wei, M.; Hong, T. MicroRNA-664 regulates cell invasion and migration and epithelial-mesenchymal transition by targeting TGF-β signal in glioblastoma. Int. J. Clin. Exp. Pathol. 2016, 9, 12361–12370. [Google Scholar]
- Shi, M.J.; Xiao, H.M.; Xie, Y.B.; Jiang, J.M.; Zhao, P.T.; Cai, G.S.; Li, Y.X.; Li, S.; Zhang, C.Z.; Cao, M.L.; et al. Differences in MicroRNA Expression in Chronic Hepatitis B Patients with Early Liver Fibrosis Based on Traditional Chinese Medicine Syndromes. Evid. Based Complement. Alternat. Med. 2020, 2020, 5956940. [Google Scholar] [CrossRef] [PubMed]
- Fort, A.; Borel, C.; Migliavacca, E.; Antonarakis, S.E.; Fish, R.J.; Neerman-Arbez, M. Regulation of fibrinogen production by microRNAs. Blood 2010, 116, 2608–2615. [Google Scholar] [CrossRef] [Green Version]
- Jin, L.; Zhang, Y.; Liang, W.; Lu, X.; Piri, N.; Wang, W.; Kaplan, H.J.; Dean, D.C.; Zhang, L.; Liu, Y. Zeb1 promotes corneal neovascularization by regulation of vascular endothelial cell proliferation. Commun. Biol. 2020, 3, 349:1–349:10. [Google Scholar] [CrossRef]
- Singh, B.; Kosuru, R.; Lakshmikanthan, S.; Sorci-Thomas, M.G.; Zhang, D.X.; Sparapani, R.; Vasquez-Vivar, J.; Chrzanowska, M. Endothelial Rap1 (Ras-Association Proximate 1) Restricts Inflammatory Signaling to Protect From the Progression of Atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2021, 41, 638–650. [Google Scholar] [CrossRef]
- Witman, M.A.; Garten, R.S.; Gifford, J.R.; Groot, H.J.; Trinity, J.D.; Stehlik, J.; Nativi, J.N.; Selzman, C.H.; Drakos, S.G.; Richardson, R.S. Further Peripheral Vascular Dysfunction in Heart Failure Patients With a Continuous-Flow Left Ventricular Assist Device: The Role of Pulsatility. JACC Heart Fail. 2015, 3, 703–711. [Google Scholar] [CrossRef]
- Dorland, Y.L.; Huveneers, S. Cell–cell junctional mechanotransduction in endothelial remodeling. Cell. Mol. Life Sci. 2017, 74, 279–292. [Google Scholar] [CrossRef] [Green Version]
- Wallez, Y.; Huber, P. Endothelial adherens and tight junctions in vascular homeostasis, inflammation and angiogenesis. Biochim. Biophys. Acta Biomembr. 2008, 1778, 794–809. [Google Scholar] [CrossRef] [Green Version]
- World Medical Association. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA 2013, 310, 2191–2194. [Google Scholar] [CrossRef] [Green Version]
- Moll, P.; Ante, M.; Seitz, A.; Reda, T. QuantSeq. 3′ mRNA sequencing for RNA quantification. Nat. Methods 2014, 11, 952. [Google Scholar] [CrossRef]
- Dlouha, D.; Blaha, M.; Blaha, V.; Fatorova, I.; Hubacek, J.A.; Stavek, P.; Lanska, V.; Parikova, A.; Pitha, J. Analysis of circulating miRNAs in patients with familial hypercholesterolaemia treated by LDL/Lp(a) apheresis. Atheroscler. Suppl. 2017, 30, 128–134. [Google Scholar] [CrossRef]
- Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J. 2011, 17, 10–12. [Google Scholar] [CrossRef]
- Langmead, B.; Trapnell, C.; Pop, M.; Salzberg, S.L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009, 10, R25. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dobin, A.; Davis, C.A.; Schlesinger, F.; Drenkow, J.; Zaleski, C.; Jha, S.; Batut, P.; Chaisson, M.; Gingeras, T.R. STAR: Ultrafast universal RNA-seq aligner. Bioinformatics 2013, 29, 15–21. [Google Scholar] [CrossRef] [PubMed]
- Liao, Y.; Smyth, G.K.; Shi, W. Featurecounts: An efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 2014, 30, 923–930. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Love, M.I.; Huber, W.; Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014, 15, 550. [Google Scholar] [CrossRef] [Green Version]
- Eden, E.; Navon, R.; Steinfeld, I.; Lipson, D.; Yakhini, Z. GOrilla: A tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinform. 2009, 10, 48. [Google Scholar] [CrossRef] [Green Version]
- Eden, E.; Lipson, D.; Yogev, S.; Yakhini, Z. Discovering motifs in ranked lists of DNA sequences. PLoS Comput. Biol. 2007, 3, e39. [Google Scholar] [CrossRef]
- Kanehisa, M.; Goto, S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000, 28, 27–30. [Google Scholar] [CrossRef] [PubMed]
- Yu, G.; Wang, L.; Han, Y.; He, Q. Clusterprofiler: An R package for comparing biological themes among gene clusters. OMICS 2012, 16, 284–287. [Google Scholar] [CrossRef] [PubMed]
miRNA | Expression | Target (s) | Function |
---|---|---|---|
miR-23b | up | TLP3, FOXO4, CHI3L1, SMAD3 | SMCs proliferation, differentiation, cytokine production |
miR-29b | up | COL1A1, COL3A1, COL5A1, ELN, MMP2, MMP9, PTEN, ADAMTS7 | ECM production, SMCs proliferation, arterial calcification, cell apoptosis |
miR-155 | up | SMAD, BCL6, CTLA4, MMP1, MMP3, SOCS, NF-κB signaling transcription factor | SMCs differentiation, regulation of inflammation |
miR-206 | up | ARF6, SLC8A1 | SMCs differentiation |
miR-34a | down | SIRT1, NOTCH | SMCs proliferation, differentiation |
miR-145 | up | KLF4/5, MYOCD, ELK1, SRF, SOX9 | SMCs differentiation, proliferation |
Inhibits TGF-β signaling, ECM production, regulation of fibrosis | |||
miR-19a/b | down | FZD4, LRP6, TLR2, TGFBRI/TGFBRII | ECs proliferation, differentiation, angiogenesis, WNT signaling pathway, regulation of fibrosis |
miR-20a | down | MKK3, TLR4 | Reduction of ECs migration and angiogenesis, TXNIP signaling, inflammation |
miR-149 | up | FGFR1, GPC1 | Regulation of angiogenic functions of ECs |
Let-7a/c/e/f | up | TGFBR3, TBX5, ADRB1, EDN1, FGF5, IL6, IκBβ | Regulation of angiogenesis of ECs and inflammation |
miR-100 | up | mTOR, NOX4 | Regulation of neovascularization |
miR-99b | up | NOX4, TGFβ | Differentiation of ECs |
miR-30c/e | up | CTGF | Promotion of the synthesis of ECM and collagen, regulation of fibrosis |
miR-142-3p | down | ADAM9, HMGB1, AZIN1, JNK1 | Regulation of fibrosis |
miR-15b/16 | down | TGF-βR1, p38, SMAD3, SMAD7, ENDOGLIN, AKT3 | Regulation of fibrosis, cell apoptosis, and angiogenesis |
miR-885 | down | ULK2 | Cell autophagic processes |
miR-511 | down | FOXC1 | Regulation of angiogenesis |
miR-664a | down | TGFBR2, AKT | Inhibits TGF-β signaling, ECM production, regulation of fibrosis |
miR-654 | down | PTEN, ATM, ADAM10, RAB22A | Regulation of fibrosis and inflammation |
N (female %) | 16 (18.8%) |
Age (years) | 49.6 ± 16.8 |
BMI (kg/m2) | 25.6 ± 5.5 |
Diabetes mellitus (%) | 1 (6.3%) |
Hypertension (%) | 8 (50%) |
Hyperlipidemia (%) | 5 (31.3%) |
CVA/TIA (%) | 0 |
NYHA classification IV (%) | 11 (68.8%) |
Etiology of nonischemic DCM (N) | 13 |
Idiopathic | 11 |
Familial | 1 |
Toxic | 1 |
Etiology of hypertrophic cardiomyopathy | 1 |
Etiology of ischemic DCM (N) | 1 |
Etiology of noncompact DCM (N) | 1 |
CRTD/ICD before LVAD implant, % | 12 (75%) |
Type of LVAD | |
Heart Mate II | 4 |
Heart Mate 3 | 12 |
Days of LVAD support (days) | 382 (325.5) |
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Dlouha, D.; Ivak, P.; Netuka, I.; Benesova, S.; Tucanova, Z.; Hubacek, J.A. An Integrative Study of Aortic mRNA/miRNA Longitudinal Changes in Long-Term LVAD Support. Int. J. Mol. Sci. 2021, 22, 7414. https://doi.org/10.3390/ijms22147414
Dlouha D, Ivak P, Netuka I, Benesova S, Tucanova Z, Hubacek JA. An Integrative Study of Aortic mRNA/miRNA Longitudinal Changes in Long-Term LVAD Support. International Journal of Molecular Sciences. 2021; 22(14):7414. https://doi.org/10.3390/ijms22147414
Chicago/Turabian StyleDlouha, Dana, Peter Ivak, Ivan Netuka, Sarka Benesova, Zuzana Tucanova, and Jaroslav A. Hubacek. 2021. "An Integrative Study of Aortic mRNA/miRNA Longitudinal Changes in Long-Term LVAD Support" International Journal of Molecular Sciences 22, no. 14: 7414. https://doi.org/10.3390/ijms22147414