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1 There is a long list of possible miRNA targets for developing miRNA-based treatments for pulmonary hypertension but few studies that have already assayed their efficacy to reverse the severity of this fatal disease. However, they have shown that it is pos + 2147 word(s) 2147 2020-05-06 13:36:32 |
2 format correct Meta information modification 2147 2020-05-11 08:12:41 |

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Carregal-Romero, S.; Fadón, L.; Berra, E.; Ruíz-Cabello, J.; Romero, S. MiRNA-Based Therapies in Pulmonary Hypertension. Encyclopedia. Available online: https://encyclopedia.pub/entry/758 (accessed on 29 March 2024).
Carregal-Romero S, Fadón L, Berra E, Ruíz-Cabello J, Romero S. MiRNA-Based Therapies in Pulmonary Hypertension. Encyclopedia. Available at: https://encyclopedia.pub/entry/758. Accessed March 29, 2024.
Carregal-Romero, Susana, Lucía Fadón, Edurne Berra, Jesús Ruíz-Cabello, Susana Romero. "MiRNA-Based Therapies in Pulmonary Hypertension" Encyclopedia, https://encyclopedia.pub/entry/758 (accessed March 29, 2024).
Carregal-Romero, S., Fadón, L., Berra, E., Ruíz-Cabello, J., & Romero, S. (2020, May 07). MiRNA-Based Therapies in Pulmonary Hypertension. In Encyclopedia. https://encyclopedia.pub/entry/758
Carregal-Romero, Susana, et al. "MiRNA-Based Therapies in Pulmonary Hypertension." Encyclopedia. Web. 07 May, 2020.
MiRNA-Based Therapies in Pulmonary Hypertension
Edit

Pulmonary hypertension involves a continuous remodeling of the pulmonary vasculature, that is similar to cancer in some aspects due to the uncontrolled proliferation of certain cells. This leads to muscularization of pulmonary vessels, development of vascular lesions, continuous vasoconstriction, and final heart failure. Current pharmacological therapies only target three molecular pathways and as a result, patients can only improve their life quality but not without suffering adverse side effects. This fatal lung disease lacks effective treatments. Therefore, there are compelling reasons to find new molecular targets and novel therapies that reverse the development of the disease. In this context, miRNA-based therapies have shown promising results that will provided in the following text while explaining the important role that had played their nanoencapsulation.

pulmonary hypertension, arteriopathy microRNA gene therapy nanoparticles smooth muscle cells endothelial cells

Pulmonary hypertension (PH) is a condition characterized by increased mean pulmonary arterial pressure. During the compensatory phase, the right ventricle of the heart deals with pressure overload to maintain the blood flow by chamber transformation. This translates into an adaptive increase in artery wall thickness which involves an uncontrolled cell proliferation. Molecular mechanisms underlying the physiopathology have not been completely elucidated but since there is no cure for this fatal disease it urges to find methodologies for the selective detection and treatment of PH.[1] PH has been classified in five different groups which depend on the origin of the disease. Pulmonary arterial hypertension (PAH) is the commonly the most studied case of PH. In PAH, the small arteries (and in some cases also the venules) in the lung are obstructed due to different reasons such as HIV infection, autoimmune disorders, and others but it can be also idiopathic. All PH groups courses with endothelium dysfunction and vascular remodeling in the lungs which has been extensively described that is accompanied by a metabolic reprogramming in the heart and the lung only explored until recently.[2][3][4] It is known that arterioles can undergo vasoconstriction imbalance, cellular remodeling, thrombosis, and cell proliferation. Pulmonary artery endothelial cells (PAECs), pulmonary artery smooth muscle cells (PASMCs), myofibroblast, pericytes, platelets, and inflammatory cells play key roles during the disease development. The vascular remodeling during PH involves PAECs dysfunction, such as proliferation, interaction with PASMCs, and transdifferentiation and the accumulation of PASMCs in obstructive vascular lesions.[5] Figure 1 shows schematically a transversal section of a pulmonary artery developing PH.

Figure 1. Schematic drawing of a transversal section of a pulmonary artery developing PH and the structural alterations in the different cellular levels. Initially smooth muscle cells excessively proliferate producing vasoconstriction. After that, inflammation, remodeling, and thrombotic lesions will follow.

miRNA Targets in Pulmonary Hypertension

Currently, PH treatments only help to relieve the symptomatology and do not stop the progression of the disease. The medical therapies available for the treatment of PAH include calcium channel blockers, endothelin receptor antagonists, phosphodiesterase type 5 inhibitors and soluble guanylate cyclase stimulators, prostacyclin analogues, and prostacyclin receptor agonists.[6] miRNA dysregulation has been correlated to the physiopathology of PH and the use of miRNA-based therapies has emerged as new hope toward the reversion of PH symptomatology.[7] Table 1 summarizes a list of reported miRNA that could be efficient therapeutic targets for the treatment of PH. In many aspects, PH disease development resembles tumorigenesis. In PH and cancer the hyperproliferative and apoptosis resistant phenotype is partially related to impaired mitochondrial dynamics and in both cases there is a metabolic dysfunction (Warburg effect) characterized by a shift from oxidative glucose metabolism to aerobic glycolysis which provides the survival conditions for highly proliferating cells.[8] Given these similarities multiple miRNAs that are aberrantly expressed in cancer are also dysregulated in PH. For instance, miR-204 and miR-205 are downregulated in pulmonary artery small muscle cells (PASMs) in PAH as well as in many cancers.[9] In both cases the downregulation of these miRNAs induces metabolic dysfunction and enhanced PASMCs proliferation. MiR-204 and miR-205-based treatments have demonstrated to be efficient for decreasing cell proliferation and metastasis in few cancers and recently it has been reported their potential use for reversing PAH in a murine model.[10][11] Its encapsulation and targeted release in the lungs could be advantageous for preventing the miRNAs being filtered by the kidney, decrease off-targeted effects, and improve intracellular delivery.

Table 1. Reported dysregulated miRNA biomarkers in pulmonary hypertension, origin of the obtained data, reported targets and miR functions.

miRNA Model Target Gene Exp. 1 Function Ref. 2
miR-9-1
+ miR-9-3
PASMCs 3 from HMM 4 HIF-1 α Phenotypic switch [12]
miR-17-5p
+ miR-20a
Bioinformatics +HEK293 cells BMPR2 Differentiation, proliferation and fibrous matrix production of PAECS 5 and PASMCs [13]
miR-100 HMM, MCT 6 mTOR Proliferation of PASMCs [14]
miR-124 HPAECs 7 PTPB1 + PKM1/M2 Proliferation of PASMCs and PAFs 8 [15]
miR-140-5p Bioinformatics (miRBase database) 23 genes & 7 signaling pathways Proliferation and pro-differentiation of PAECS, PASMCs & PAFs [16]
miR-145 HMM, HPASMC BMPR2 Proliferation of PASMCs [17]
miR-199a-5p HPASMCs, HPAECs & HMM SMAD3 Inhibit the level of NO and promote the concentration of Ca2+ [18]
miR-204 PAECs TGFBR2, α-SMA, SMAD2/7 Proliferation and migration of PAECs [19]
miR-205-5p Hypoxic PASMCs & HMM MICAL2
ERK1/2 signaling
Proliferation of PASMCs [11]
miR-206 PASMCs & HMM HIF-1 α /FHL-1 Promotion of cell entry into the S phase and PASMC proliferation [20]
miR-214 Hypoxic HPASMCs, Sugen/HMM CCNL2, LMOD1, MEF2C, PTEN Proliferation of PASMCs by suppressing cell apoptosis [21]
miR-339 MCT murine model FGF Proliferation of PASMC [22]
miR-449a-5p PASMCs from MCT MYC Mitochondrial dysfunction and proliferation of PASMCs [23]
miR-1281 Hypoxic HPASMCs & MCT HDAC4 Cell proliferation and migration [24]
miR-637 HPASMCs CDK6 Increase PASMCs viability [25]
miR-4632 HPASMCs JUN Inhibit proliferation and promote HPASMCs apoptosis [26]

Table 2shows a small portion of the possible miRNA targets and some of their reported targeted genes that could be used to treat PH. Considering that only for dysfunctional PAECs more than 20 different dysregulated miRNAs have been already reported, it will become essential to use in silico approaches to identify the most relevant miRNA targets for developing novel treatments against PAH [27]. In this context, we referred readers to the work recently published by Bonnet et al. [28].

miRNA-based therapies for Pulmonary Hypertension

Currently, the treatment of PH with miRNA-based therapies is still in an early phase, similar to siRNA-based therapies [29]. There are no clinical trials going on yet, but fortunately all reported pre-clinical trials up to now have shown significant beneficial effects and some of them have demonstrated an evident decrease of the arteriopathy and cardiac dysfunction. We have collected these examples in Table 2.

Table 2. Relevant information about miRNA-based therapies in pulmonary hypertension.

1 Nanovector. 2 Administration. 3 Reference. 4 Intravenous injection. 5 Inhibition therapy. 6 Right Ventricle Preassure. 7 Right Ventricle Hypertrophy. 8 Monocrotaline murine model. 9 Hypoxic murine model. 10 Hypoxic murine knockout model. 11 Subcutaneous injection. 12 Nanoparticles. 13 Replacement therapy. 14 Intratracheal nebulization. ↑ means increase and ↓ means decrease.

As can be seen in Table 2, some studies aimed at determining the possible therapeutic effect of a target miRNA using bare miRNA mimics or Antagomirs as a first assay. This was the case of the study carried out by Pullamsetti et al. in 2012. However, most of the reported research has been done using nanovectors known to improve transfection efficiency such as commercial lipofectamine or viral vectors [11][34]. For instance, in the study of the potential use of miR-145 as a therapeutic target, Caruso et al. was first evidencing the upregulation of miR-145 in humans with PAH and in animal models of PAH. Then, they used antimiR-145 delivered with commercial lipofectamine and showed that it prevented arteriopathy in hypoxic mice. Owing to this study, some years later McLendon et al. reported effective delivery and retention in the lungs of antimiR-145 loaded in more sophisticated cationic liposome-based nanovectors made of polymer-functionalized lipopolyamines that provided stealth properties [[32]]. Importantly, their results showed an evident decrease of right ventricle pressure, decreased artery muscularization, and lower degree of cardiac dysfunction in murine models of severe PAH while avoiding off-target effects and toxicity. These two last features are essential for the translation of miRNA therapies into clinics but they are still a challenge in the field.

The dose of miRNA required to obtain a therapeutic effect depends on the animal model of PH and many other factors. However, we could draw some general conclusions from Table 2. Comparing two different miRNA therapies in mice housed in hypoxic conditions, reduction of arteriopathy could be achieved in both cases after 2–3 intravenous injections per week for 2 weeks (6 injections in total) [33]. When miRNAs were not encapsulated, a higher concentration in treatment, 8 mg/Kg as compared with 2 mg/Kg, was required for the administration of Invivofectamine. In rat models with monocrotaline-induced PH or hypoxia and Sugen, the therapeutic effect was achieved only after 2–3 intravenous injections. Similarly, the concentration of miRNA from the injections was lower for encapsulated therapies (2 mg/Kg vs. 5 mg/Kg) [32][31]. The dose could also decrease with direct administration to the lungs, as demonstrated by Courboulin et al. [10]. Only two nebulizations (1 per week) of encapsulated miRNA mimics were required to obtain a therapeutic outcome of miR-204a mimics in a PH model with monocrotaline. This administration method could also avoid some of the potential off-target effects of miRNA-based therapies, but this has not yet been confirmed. Despite the lungs offer the advantage of local delivery of therapies, as can be seen in Table 2, the majority of the miRNA treatments are currently being administered intravenously. This is due to the early stage of these therapies and the barriers that still remain for real targeted therapies such as (1) controlling lung clearance, (2) achieving a homogeneous biodistribution, (3) obtaining stable miRNA carriers for nebulization, and (4) obtaining selective delivery systems to the target cells. In addition, what is not yet known is whether the decrease in PH pathology is temporary or lasting [35]. Future advances in other miRNA therapies such as cancer are likely to help address these challenges for PH [36].

In the field of non-coding RNA therapies, combination therapies are expected to be more efficient than single-target RNA; Sindi et al. have obtained outstanding results in this direction already in PH [33]. These authors first focused their work on deciphering whether the Krüppel-like factor 2 (KLF2) signaling pathway in PAECs could be a novel molecular target to combat PH. They then demonstrated that the combination therapy of exosomal miR-181a-5p and miR-324-5p was helpful in reducing right ventricle pressure and hypertrophy, cell proliferation and angiogenesis in murine models. Interestingly, they compared single miRNA delivery with combination therapy displaying a higher efficiency for the latter. This study, in addition shows the potential use of exosomes as efficient carriers for miRNA-based therapies, illustrates perfectly how important is to detect many different miRNAs to find the best therapeutic outcome.

Figure 2depicts the few but promising nanovectors applied to date to treat PH with miRNA therapies and their reported cell targets (also reported in Table 2). Nanovectors may target PASMCs because of dysfunctional endothelium patency in HP [37]. However, the use of nanovectors functionalized with targeting molecules could show significant improvements to avoid side and off-target effects while improving therapeutic outcomes. Peptides and antibodies have been already applied successfully in miRNA-based therapies when targeting other organs such as heart or liver [38][39][40][41], so we are convinced that this strategy will be promptly applied in PH treatments. There is plenty of room for improvement in miRNA therapeutics for PH.

Figure 2. Schematic drawing of a cross section of two pulmonary arteries that develop PH and are being treated with nanopharmaceuticals (represented as small red and black spheres) that target the endothelial cells of the PAEC arteries (A) or smooth muscle cells PASMC (B). Endothelial dysfunction leads to a patent state in which NPs can leak into the pulmonary vasculature and reach PASMC more easily than in healthy arteries. The nanovectors collected in Table 2 are shown here.

References

  1. Stephen L. Archer; E. Kenneth Weir; Martin R. Wilkins; The Basic Science of Pulmonary Arterial Hypertension for Clinicians: new concepts and experimental therapies. Circulation 2010, 121, 2045-2066, 10.1161/CIRCULATIONAHA.108.847707.
  2. Rohit Budhiraja; Rubin M. Tuder; Paul M. Hassoun; Endothelial Dysfunction in Pulmonary Hypertension. Circulation 2004, 109, 159-165, 10.1161/01.cir.0000102381.57477.50.
  3. Jose L. Izquierdo-Garcia; Teresa Arias; Yeny Rojas; Victoria Garcia-Ruiz; Arnoldo Santos; Silvia Martin-Puig; Jesús Ruíz-Cabello; Metabolic Reprogramming in the Heart and Lung in a Murine Model of Pulmonary Arterial Hypertension. Frontiers in Cardiovascular Medicine 2018, 5, 110, 10.3389/fcvm.2018.00110.
  4. José Luis Izquierdo-García; Lucia Fadon; Marta Beraza; Unai Cossio; Jordi Llop; Jesus Ruiz-Cabello; In-vivo lung molecular imaging of choline metabolism in a rat model of pulmonary arterial hypertension. Pulmonary hypertension 2019, 54, PA1422, 10.1183/13993003.congress-2019.pa1422.
  5. Benoît Ranchoux; Fabrice Antigny; Catherine Rucker-Martin; Aurélie Hautefort; Christine Péchoux; Harm Jan Bogaard; Peter Dorfmüller; S. Remy; Florence Lecerf; Sylvie Planté; et al.Sophie ChatElie FadelAmal HoussainiIgnacio AnegonS. AdnotG. SimonneauMarc HumbertSylvia Cohen-KaminskyFrédéric Perros Endothelial-to-Mesenchymal Transition in Pulmonary Hypertension. Circulation 2015, 131, 1006-1018, 10.1161/circulationaha.114.008750.
  6. Marc Humbert; Hossein Ardeschir Ghofrani; The molecular targets of approved treatments for pulmonary arterial hypertension. Thorax 2015, 71, 73-83, 10.1136/thoraxjnl-2015-207170.
  7. Hyung J. Chun; Sébastien Bonnet; Stephen Y. Chan; Translational Advances in the Field of Pulmonary Hypertension.Translating MicroRNA Biology in Pulmonary Hypertension. It Will Take More Than “miR” Words. American Journal of Respiratory and Critical Care Medicine 2017, 195, 167-178, 10.1164/rccm.201604-0886PP.
  8. Carlyne D Cool; Wolfgang Michael Kuebler; Harm Jan Bogaard; Edda Spiekerkoetter; Mark R. Nicolls; Norbert F Voelkel; The Hallmarks of Severe Pulmonary Arterial Hypertension: The Cancer Hypothesis - Ten years later.. American Journal of Physiology-Lung Cellular and Molecular Physiology 2020, _, _, 10.1152/ajplung.00476.2019.
  9. Ying Shi; Jianjun Huang; Jun Zhou; Ying Liu; Xiaodan Fu; Yimin Li; Gang Yin; Jifang Wen; MicroRNA-204 inhibits proliferation, migration, invasion and epithelial-mesenchymal transition in osteosarcoma cells via targeting Sirtuin 1. Oncology Reports 2015, 34, 399-406, 10.3892/or.2015.3986.
  10. A. Courboulin; R. Paulin; N. J. Giguere; N. Saksouk; T. Perreault; J. Meloche; E. R. Paquet; S. Biardel; S. Provencher; J. Côté; et al.M. J. SimardS. Bonnet Role for miR-204 in human pulmonary arterial hypertension. Journal of Cell Biology 2011, 192, 535–548, 10.1083/jcb1924oia4.
  11. Wei Tao; Weiming Sun; Hailong Zhu; Jiayi Zhang; miR-205-5p suppresses pulmonary vascular smooth muscle cell proliferation by targeting MICAL2-mediated Erk1/2 signaling.. Microvascular Research 2019, 124, 43-50, 10.1016/j.mvr.2019.03.001.
  12. Fabo Shan; Junxia Li; Qing-Yuan Huang; HIF-1 Alpha-Induced Up-Regulation of miR-9 Contributes to Phenotypic Modulation in Pulmonary Artery Smooth Muscle Cells During Hypoxia. Journal of Cellular Physiology 2014, 229, 1511-1520, 10.1002/jcp.24593.
  13. Matthias Brock; Michelle Trenkmann; Renate E. Gay; Beat A. Michel; Steffen Gay; Manuel Fischler; Silvia Ulrich; Rudolf Speich; Lars C. Huber; Interleukin-6 Modulates the Expression of the Bone Morphogenic Protein Receptor Type II Through a Novel STAT3-microRNA Cluster 17/92 Pathway. Circulation Research 2009, 104, 1184-1191, 10.1161/circresaha.109.197491.
  14. Ai-Ping Wang; Xiao-Hui Li; Shao-Xin Gong; Wen-Qun Li; Chang-Ping Hu; Zheng Zhang; Yuan-Jian Li; miR-100 suppresses mTOR signaling in hypoxia-induced pulmonary hypertension in rats. European Journal of Pharmacology 2015, 765, 565-573, 10.1016/j.ejphar.2015.09.031.
  15. Caruso, P.; Dunmore, B.J.; Schlosser, K.; Schoors, S.; Dos Santos, C.C.; Perez-Iratxeta, C.; Lavoie, J.R.; Zhang, H.; Long, L.; Flockton, A.R.; et al.et al. miR-100 suppresses mTOR signaling in hypoxia-induced pulmonary hypertension in rats. Circulation 2017, 136, 2451–2467.
  16. Fangwei Li; Wenhua Shi; Yixin Wan; Qingting Wang; Wei Feng; Xin Yan; Jian Wang; Limin Chai; Qianqian Zhang; Manxiang Li; et al. Prediction of target genes for miR‐140‐5p in pulmonary arterial hypertension using bioinformatics methods. FEBS Open Bio 2017, 7, 1880-1890, 10.1002/2211-5463.12322.
  17. Lars C Huber; Matthias Brock; Caruso P; Dempsie Y; Stevens Hc; McDonald Ra; Long L; Lu R; White K; Mair Km; et al.McClure JdSouthwood MUpton PXin MVan Rooij EOlson EnMorrell NwMac LeanBaker Ah Faculty Opinions recommendation of A role for miR-145 in pulmonary arterial hypertension: evidence from mouse models and patient samples.. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature 2012, 111, 290–300, 10.3410/f.717397860.792802857.
  18. Yuanhua Liu; Guanghui Liu; Hui Zhang; Jing Wang; MiRNA-199a-5p influences pulmonary artery hypertension via downregulating Smad3. Biochemical and Biophysical Research Communications 2016, 473, 859-866, 10.1016/j.bbrc.2016.03.140.
  19. Hua Yu; Min Xu; Yizhi Dong; Jingjing Liu; Yaozhe Li; Wei Mao; Jindan Wang; Liangxing Wang; 1,25(OH) 2 D 3 attenuates pulmonary arterial hypertension via microRNA-204 mediated Tgfbr2/Smad signaling. Experimental Cell Research 2018, 362, 311-323, 10.1016/j.yexcr.2017.11.032.
  20. Samuel Jalali; Gurukumar K. Ramanathan; Prasanna Tamarapu Parthasarathy; Salman Aljubran; Lakshmi Galam; Asfiya Yunus; Sara García; Ruan R. Cox; Richard F. Lockey; Narasaiah Kolliputi; et al. Mir-206 Regulates Pulmonary Artery Smooth Muscle Cell Proliferation and Differentiation. PLOS ONE 2012, 7, e46808, 10.1371/journal.pone.0046808.
  21. Liu, H.; Tao, Y.; Chen, M.; Yu, J.; Li, W.-J.; Tao, L.; Li, Y.; Li, F.; Upregulation of MicroRNA-214 Contributes to the Development of Vascular Remodeling in Hypoxia-induced Pulmonary Hypertension Via Targeting CCNL2. Sci. Rep. 2016, 6, 24661.
  22. Jidong Chen; Xiaolei Cui; Li Li; Junle Qu; J. Usha Raj; Deming Gou; MiR‐339 inhibits proliferation of pulmonary artery smooth muscle cell by targeting FGF signaling. Physiological Reports 2017, 5, e13441, 10.14814/phy2.13441.
  23. Chen Zhang; Cui Ma; Lixin Zhang; Linlin Zhang; Fengying Zhang; Mingfei Ma; Xiaodong Zheng; Min Mao; Tingting Shen; Daling Zhu; et al. MiR-449a-5p mediates mitochondrial dysfunction and phenotypic transition by targeting Myc in pulmonary arterial smooth muscle cells. Journal of Molecular Medicine 2019, 97, 409-422, 10.1007/s00109-019-01751-7.
  24. Yanjiao Li; Li Li; Zhengjiang Qian; Boya Lin; Jidong Chen; Yixuan Luo; Junle Qu; J. Usha Raj; Deming Gou; Phosphatidylinositol 3‐Kinase–DNA Methyltransferase 1–miR‐1281–Histone Deacetylase 4 Regulatory Axis Mediates Platelet‐Derived Growth Factor–Induced Proliferation and Migration of Pulmonary Artery Smooth Muscle Cells. Journal of the American Heart Association 2018, 7, e007572, 10.1161/jaha.117.007572.
  25. Hai-Yan Sang; Yingli Jin; Wen-Qi Zhang; Li-Bo Chen; Downregulation of microRNA-637 Increases Risk of Hypoxia-Induced Pulmonary Hypertension by Modulating Expression of Cyclin Dependent Kinase 6 (CDK6) in Pulmonary Smooth Muscle Cells.. Medical Science Monitor 2016, 22, 4066–4072.
  26. Zhengjiang Qian; Yanjiao Li; Jidong Chen; Xiang Li; Deming Gou; miR-4632 mediates PDGF-BB-induced proliferation and antiapoptosis of human pulmonary artery smooth muscle cells via targeting cJUN. American Journal of Physiology-Cell Physiology 2017, 313, C380-C391, 10.1152/ajpcell.00061.2017.
  27. Gaetano Santulli; MicroRNAs and Endothelial (Dys) Function.. Journal of Cellular Physiology 2015, 231, 1638-1644, 10.1002/jcp.25276.
  28. Sebastien Bonnet; Olivier Boucherat; Roxane Paulin; Danchen Wu; Charles C. T. Hindmarch; Stephen L. Archer; Rui Song; Joseph B. Moore; Steeve Provencher; Lubo Zhang; et al.Shizuka Uchida Clinical value of non-coding RNAs in cardiovascular, pulmonary, and muscle diseases. American Journal of Physiology-Cell Physiology 2020, 318, C1-C28, 10.1152/ajpcell.00078.2019.
  29. Cheuk-Kwan Sun; Yen-Yi Zhen; Hung-I Lu; Pei-Hsun Sung; Li-Teh Chang; Tzu-Hsien Tsai; Jiunn-Jye Sheu; Yung-Lung Chen; Sarah Chua; Hsueh-Wen Chang; et al.Yi-Ling ChenFan-Yen LeeHon-Kan Yip Reducing TRPC1 Expression through Liposome-Mediated siRNA Delivery Markedly Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension in a Murine Model. Stem Cells International 2014, 2014, 1-19, 10.1155/2014/316214.
  30. Soni Savai Pullamsetti; Carmen Doebele; Ariane Fischer; Rajkumar Savai; Baktybek Kojonazarov; Bhola K. Dahal; Hossein Ardeschir Ghofrani; Norbert Weissmann; Friedrich Grimminger; Angelika Bonauer; et al.Werner SeegerAndreas M. ZeiherStefanie DimmelerRalph T. Schermuly Inhibition of MicroRNA-17 Improves Lung and Heart Function in Experimental Pulmonary Hypertension. American Journal of Respiratory and Critical Care Medicine 2012, 185, 409-419, 10.1164/rccm.201106-1093oc.
  31. Tianji Chen; Guofei Zhou; Qiyuan Zhou; Haiyang Tang; Joyce Christina F. Ibe; Hongqiang Cheng; Deming Gou; Ju Chen; Jason X.-J. Yuan; J. Usha Raj; et al. Loss of MicroRNA-17∼92 in Smooth Muscle Cells Attenuates Experimental Pulmonary Hypertension via Induction of PDZ and LIM Domain 5. American Journal of Respiratory and Critical Care Medicine 2015, 191, 678-692, 10.1164/rccm.201405-0941oc.
  32. Jared McLendon; Sachindra R. Joshi; Jeff Sparks; Majed Matar; Jason G. Fewell; Kohtaro Abe; Masahiko Oka; Ivan F. McMurtry; William Gerthoffer; Lipid nanoparticle delivery of a microRNA-145 inhibitor improves experimental pulmonary hypertension.. Journal of Controlled Release 2015, 210, 67-75, 10.1016/j.jconrel.2015.05.261.
  33. Hebah A. Sindi; Giusy Russomanno; Sandro Satta; Vahitha B. Abdul-Salam; Kyeong Beom Jo; Basma Qazi-Chaudhry; Alexander J. Ainscough; Robert Szulcek; Harm Jan Bogaard; Claire C. Morgan; et al.Soni Savai PullamsettiMai M. AlzaydiChristopher J. RhodesRoberto PivaChristina A. EichstaedtEkkehard GrünigMartin R WilkinsBeata Wojciak-Stothard Therapeutic potential of KLF2-induced exosomal microRNAs in pulmonary hypertension.. Nature Communications 2020, 11, 1185-1217, 10.1038/s41467-020-14966-x.
  34. Jie Fu; Peiyuan Bai; Yiwei Chen; Tingting Yu; Fen Li; Inhibition of miR-495 Improves Both Vascular Remodeling and Angiogenesis in Pulmonary Hypertension.. Journal of Vascular Research 2019, 56, 97-106, 10.1159/000500024.
  35. Chiranjib Chakraborty; Ashish Ranjan Sharma; Garima Sharma; C. George Priya Doss; Sang-Soo Lee; Therapeutic miRNA and siRNA: Moving from Bench to Clinic as Next Generation Medicine. Molecular Therapy - Nucleic Acids 2017, 8, 132-143, 10.1016/j.omtn.2017.06.005.
  36. Wei Yin; Mark Rogge; TargetingRNA: A Transformative Therapeutic Strategy. Clinical and Translational Science 2019, 12, 98-112, 10.1111/cts.12624.
  37. Victor Segura-Ibarra; Javier Amione-Guerra; Ana Sofia Cruz-Solbes; Francisca E. Cara; David A. Iruegas-Nunez; Suhong Wu; Keith A. Youker; Arvind Bhimaraj; Guillermo Torre-Amione; Mauro Ferrari; et al.Harry Karmouty-QuintanaAshrith GuhaElvin Blanco Rapamycin nanoparticles localize in diseased lung vasculature and prevent pulmonary arterial hypertension. International Journal of Pharmaceutics 2017, 524, 257-267, 10.1016/j.ijpharm.2017.03.069.
  38. Zhiman Bai; Jing Wei; Changmin Yu; Xisi Han; Xiaofei Qin; Chengwu Zhang; Tiantian Zhang; Lin Li; Wei Huang; Non-viral nanocarriers for intracellular delivery of microRNA therapeutics.. Journal of Materials Chemistry B 2019, 7, 1209-1225, 10.1039/c8tb02946f.
  39. Michele Miragoli; Paola Ceriotti; Michele Iafisco; Marco Vacchiano; Nicolò Salvarani; Alessio Alogna; Pierluigi Carullo; Gloria Belén Ramírez-Rodríguez; Tatiana Patrício; Lorenzo Degli Esposti; Francesca Rossi; F Ravanetti; Silvana Pinelli; Rossella Alinovi; Marco Erreni; Stefano Rossi; Gianluigi Condorelli; Heiner Post; Anna Tampieri; Daniele Catalucci; Inhalation of peptide-loaded nanoparticles improves heart failure. Science Translational Medicine 2018, 10, eaan6205, 10.1126/scitranslmed.aan6205.
  40. Kulakovskii, V.D.; Bacher, G.; Weigand, R.; Kümmell, T.; Forchel, A.; Borovitskaya, E.; Leonardi, K.; Hommel, S. Fins Structure of Biexction Emission in Symmetric and Aymmetric CdSe/ZnSe Singel Quantum Dots. Phys. Rev. Lett. 1999, 82, 1780–1783.
  41. Adrian Gabriel Torres; Martin M. Fabani; Elena Vigorito; Nna Williams; Naowras Al-Obaidi; Filip Wojciechowski; Robert H. E. Hudson; Oliver Seitz; Michael J. Gait; Chemical structure requirements and cellular targeting of microRNA-122 by peptide nucleic acids anti-miRs.. Nucleic Acids Research 2011, 40, 2152-67, 10.1093/nar/gkr885.
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