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Heart, Lung and Circulation

The Functions of Long Non-Coding RNA (lncRNA) H19 in the Heart

  • Author Footnotes
    1 Contributed equally.
    Yao Wang
    Footnotes
    1 Contributed equally.
    Affiliations
    Shandong Institute of Endocrine and Metabolic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
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  • Author Footnotes
    1 Contributed equally.
    Xiaojing Sun
    Footnotes
    1 Contributed equally.
    Affiliations
    Department of Geriatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
    Search for articles by this author
  • Xianglan Sun
    Correspondence
    Corresponding author at: Department of Geriatrics, Department of Geriatric Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
    Affiliations
    Department of Geriatrics, Department of Geriatric Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
    Search for articles by this author
  • Author Footnotes
    1 Contributed equally.
Published:November 25, 2021DOI:https://doi.org/10.1016/j.hlc.2021.10.022
      Cardiovascular diseases (CVDs) are major causes of morbidity and mortality worldwide. Great effort has been put into exploring early diagnostic biomarkers and innovative therapeutic strategies for preventing CVD progression over the last two decades. Long non-coding RNAs (lncRNAs) have been identified as novel regulators in cardiac development and cardiac pathogenesis. For example, lncRNA H19 (H19), also known as a fetal gene abundant in adult heart and skeletal muscles and evolutionarily conserved in humans and mice, has a regulatory role in aortic aneurysm, myocardial hypertrophy, extracellular matrix reconstitution, and coronary artery diseases. Yet, the exact function of H19 in the heart remains unknown. This review summarises the functions of H19 in the heart and discusses the challenges and possible strategies of H19 research for cardiovascular disease.

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      References

        • Wang Y.
        • Sun X.
        The Functions of LncRNA in the heart.
        Diabetes Res Clin Pract. 2020; : 108249
        • Prestes P.R.
        • Maier M.C.
        • Woods B.A.
        • Charchar F.J.
        A Guide to the short, long and circular RNAs in hypertension and cardiovascular disease.
        Int J Mol Sci. 2020; 21: 3666
        • Han P.
        • Li W.
        • Lin C.H.
        • Yang J.
        • Shang C.
        • Nuerenberg S.T.
        • et al.
        A long noncoding RNA protects the heart from pathological hypertrophy.
        Nature. 2014; 514: 102-106
        • Viereck R.
        • Kumarswamy A.
        • Foinquinos A.
        • Xiao K.
        • Avramopoulos P.
        • Kunz M.
        • et al.
        Long noncoding RNA Chast promotes cardiac remodeling.
        Sci Transl Med. 2016; 8
        • Wang K.
        • Liu F.
        • Zhou L.-Y.
        • Long B.
        • Yuan S.-M.
        • Liu C.-Y.
        • et al.
        The long noncoding RNA CHRF regulates cardiac hypertrophy by targeting miR-489.
        Circ Res. 2014; 114: 1377-1388
        • Jiang F.
        • Zhou X.
        • Huang J.
        Long non-coding RNA-ROR mediates the reprogramming in cardiac hypertrophy.
        PLoS ONE. 2016; 4: 11
        • Liu L.
        • An X.
        • Li Z.
        • Song Y.
        • Li L.
        • Zuo S.
        • et al.
        The H19 long noncoding RNA is a novel negative regulator of cardiomyocyte hypertrophy.
        Cardiovasc Res. 2016; 111: 56-65
        • Lv L.
        • Li T.
        • Li X.
        • Xu C.
        • liu Q.
        • Jiang H.
        • et al.
        The lncRNA Plscr4 controls cardiac hypertrophy by regulating miR-214.
        Mol Ther Nucleic Acids. 2018; 10: 387-397
        • Zhu X.-H.
        • Yuan Y.-X.
        • Rao S.-L.
        • Wang P.
        LncRNA MIAT enhances cardiac hypertrophy partly through sponging miR-150.
        Eur Rev Med Pharmacol Sci. 2016; 20: 3653-3660
        • Wang K.
        • Long B.
        • Zhou L.-Y.
        • Liu F.
        • Zhou Q.-Y.
        • Fan Y.-Y.
        • et al.
        CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation.
        Nat Comm. 2014; 5: 3596
        • Wang S.
        • Yu W.
        • Chen J.
        • Yao T.
        • Deng F.
        LncRNA MALAT1sponges miR-203 to promote inflammation in myocardial ischemia-reperfusion injury.
        Int J Cardiol. 2018; 268
        • Li L.
        • Zhang M.
        • Chen W.
        • Wang R.
        • Ye Z.
        • Wang Y.
        • et al.
        LncRNA-HOTAIR inhibition aggravates oxidative stress-induced H9c2 cells injury through suppression of MMP2 by miR-125.
        Acta Biochim Biophys Sin. 2018; 50: 996-1006
        • Chen J.
        • Hu Q.
        • Zhang B.F.
        • Liu X.P.
        • Yang S.
        • Jiang H.
        Long noncoding RNA UCA1 inhibits ischaemia/reperfusion injury induced cardiomyocytes apoptosis via suppression of endoplasmic reticulum stress.
        Genes Genom. 2019; 41: 803-810
        • Zhou T.
        • Qin G.
        • Yang L.
        • Xiang D.
        • Li S.
        LncRNA XIST regulates myocardial infarction by targeting miR-130a-3p.
        J Cell Physiol. 2019; 234: 8659-8667
        • Wang K.
        • Liu F.
        • Liu C.-Y.
        • An T.
        • Zhang J.
        • Zhou L.-Y.
        • et al.
        The long noncoding RNA NRF regulates programmed necrosis and myocardial injury during ischemia and reperfusion by targeting miR-873.
        Cell Death Differ. 2016; 23: 1394-1405
        • Wang J.-X.
        • Zhang X.-J.
        • Li Q.
        • Wang K.
        • Wang Y.
        • Jiao J.-Q.
        • et al.
        MicroRNA-103/107 regulate programmed necrosis and myocardial ischemia/reperfusion injury through targeting FADD.
        Circ Res. 2015; 117: 352-363
        • Zhou H.
        • Wang B.
        • Yang Y.-X.
        • Jia Q.-J.
        • Zhang A.
        • Qi Z.-W.
        • et al.
        Long noncoding RNAs in pathological cardiac remodeling: a review of the update literature.
        Biomed Res Int. 2019; : 7159592
        • Bitarafan S.
        • Yari M.
        • Broumand M.A.
        • Hossein Ghaderian S.M.
        • Rahimi M.
        • Mirfakhraie R.
        • et al.
        Association of increased levels of lncRNA H19 in PBMCs with risk of coronary artery disease.
        Cell J. 2019; 20: 564-568
        • Zhang Z.
        • Gao W.
        • Long Q.-Q.
        • Zhang J.
        • Li Y.-F.
        • Liu D.-C.
        • et al.
        Increased plasma levels of lncRNA H19 and LIPCAR are associated with increased risk of coronary artery disease in a Chinese population.
        Sci Rep. 2017; 7: 7491
        • Gibb E.A.
        • Brown C.J.
        • Lam W.L.
        The functional role of long non-coding RNA in human carcinomas.
        Mol Cancer. 2011; 10: 38
        • Gao Y.
        • Wu F.
        • Zhou J.
        • Yan L.
        • Jurczak M.J.
        • Lee H.-Y.
        • et al.
        The H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells.
        Nucleic Acids Res. 2014; 42: 13799-13811
        • Kallen A.N.
        • Zhou X.-B.
        • Xu J.
        • Qiao C.
        • Ma J.
        • Yan L.
        • et al.
        The imprinted H19 lncRNA antagonizes let-7 microRNAs.
        Mol Cell. 2013; 52: 101-112
        • Gao W.
        • Zhu M.
        • Wang H.
        • Zhao S.
        • Zhao D.
        • Yang Y.
        • et al.
        Association of polymorphisms in long non-coding RNA H19 with coronary artery disease risk in a Chinese population.
        Mutat Res. 2015; 772: 15-22
        • Lee D.F.
        • Su J.
        • Kim H.S.
        • Chang B.
        • Papatsenko D.
        • Zhao R.
        • et al.
        Modeling familial cancer with induced pluripotent stem cells.
        Cell. 2015; 161: 240-254
        • Eun B.
        • Sampley M.L.
        • Van Winkle M.T.
        • Good A.L.
        • Kachman M.M.
        • Pfeifer K.
        The Igf2/H19 muscle enhancer is an active transcriptional complex.
        Nucleic Acids Res. 2013; 41: 8126-8134
        • Li H.
        • Zhu H.
        • Ge J.
        Long noncoding RNA: recent updates in atherosclerosis.
        Int J Biol Sci. 2016; 12: 898-910
        • Ballantyne M.D.
        • McDonald R.A.
        • Baker A.H.
        lncRNA/MicroRNA interactions in the vasculature.
        Clin Pharmacol Ther. 2016; 99: 494-501
        • Moorman A.F.M.
        • Christoffels V.M.
        Cardiac chamber formation: development, genes, and evolution.
        Physiol Rev. 2003; 83: 1223-1267
        • Moorman A.F.M.
        • Soufan A.T.
        • Hagoort J.
        • de Boer P.A.J.
        • Christoffels V.M.
        Development of the building plan of the heart.
        Ann NY Acad Sci. 2004; 1015: 171-181
        • García-Padilla C.
        • Domínguez J.N.
        • Aránega A.E.
        • Franco D.
        Differential chamber-specific expression and regulation of long noncoding RNAs during cardiac development.
        Biochim Biophys Acta Gene Regul Mech. 2019; 1862: 194435
        • Nascone N.
        • Mercola M.
        An inductive role for the endoderm in Xenopus cardiogenesis.
        Development. 1995; 121: 515-523
        • Monzen K.
        • Shiojima I.
        • Hiroi Y.
        • Kudoh S.
        • Oka T.
        • Takimoto E.
        • et al.
        Bone morphogenetic proteins induce cardiomyocyte differentiation through the mitogen-activated protein kinase kinase kinase TAK1 and cardiac transcription factors Csx/Nkx-2.5 and GATA-4.
        Mol Cell Biol. 1999; 19: 7096-7105
        • Gabory A.
        • Ripoche M.-A.
        • Le Digarcher A.
        • Watrin F.
        • Ziyyat A.
        • Forné T.
        • et al.
        H19 acts as a trans regulator of the imprinted gene network controlling growth in mice.
        Development. 2009; 136: 3413-3421
        • Han Y.
        • Xu H.
        • Cheng J.
        • Zhang Y.
        • Gao C.
        • Fan T.
        • et al.
        Downregulation of long non-coding RNA H19 promotes P19CL6 cells proliferation and inhibits apoptosis during late-stage cardiac differentiation via miR-19b-modulated Sox6.
        Cell Biosci. 2016; 6: 58
        • Nunes M.C.P.
        • Guimarães Júnior M.H.
        • Diamantino A.C.
        • Gelape C.L.
        • Ferrari T.C.A.
        Cardiac manifestations of parasitic diseases.
        Heart. 2017; 103: 651-658
        • Rathod R.H.
        • Powell A.J.
        • Geva T.
        Myocardial fibrosis in congenital heart disease.
        Circ J. 2016; 80: 1300-1307
        • Tang Y.
        • He R.
        • An J.
        • Deng P.
        • Huang L.
        • Yang W.
        The effect of H19-miR-29b interaction on bleomycin induced mouse model of idiopathic pulmonary fibrosis.
        Biochem Biophys Res Commun. 2016; 479: 417-423
        • Tao H.
        • Cao W.
        • Yang J.-J.
        • Shi K.-H.
        • Zhou X.
        • Liu L.-P.
        • et al.
        Long noncoding RNA H19 controls DUSP5/ERK1/2 axis in cardiac fibroblast proliferation and fibrosis.
        Cardiovasc Pathol. 2016; 25: 381-389
        • Xie H.
        • Xue J.-D.
        • Chao F.
        • Jin Y.-F.
        • Fu Q.
        Long non-coding RNA-H19 antagonism protects against renal fibrosis.
        Oncotarget. 2016; 7: 51473-51481
        • Huang Z.-W.
        • Tian L.-H.
        • Yang B.
        • Guo R.-M.
        Long noncoding RNA h19 acts as a competing endogenous RNA to mediate CTGF expression by sponging miR-455 in cardiac fibrosis.
        DNA Cell Biol. 2017; 36: 759-766
        • Reed G.W.
        • Rossi J.E.
        • Cannon C.P.
        Acute myocardial infarction.
        Lancet. 2017; 389: 197-210
        • Zhou M.
        • Zou Y.-G.
        • Xue Y.-Z.
        • Wang X.-H.
        • Gao H.
        • Dong H.-W.
        • et al.
        Long non-coding RNA H19 protects acute myocardial infarction through activating autophagy in mice.
        Eur Rev Med Pharmacol Sci. 2018; 22: 5647-5651
        • Borer J.S.
        • Truter S.
        • Herrold E.M.
        • Falcone D.J.
        • Pena M.
        • Carter J.N.
        • et al.
        Myocardial fibrosis in chronic aortic regurgitation: molecular and cellular responses to volume overload.
        Circulation. 2002; 105: 1837-1842
        • Pfeiffer M.A.
        • Braunwald E.
        Ventricular remodeling afer myocardial infarction: experimental observations and clinical implications.
        Circulation. 1990; 81: 1161-1172
        • Lee J.-H.
        • Gao C.
        • Peng G.
        • Greer C.
        • Ren S.
        • Wang Y.
        • et al.
        Analysis of transcriptome complexity through RNA sequencing in normal and failing murine hearts.
        Circ Res. 2011; 109: 1332-1341
        • Choong O.K.
        • Chen C.-Y.
        • Zhang J.
        • Lin J.-H.
        • Lin P.-J.
        • Ruan S.-C.
        • et al.
        Hypoxia-induced H19/YB-1 cascade modulates cardiac remodeling after infarction.
        Theranostics. 2019; 9: 6550-6567
        • Farsangi S.J.
        • Rostamzadeh F.
        • Sheikholeslami M.
        • Jafari E.
        • Karimzadeh M.
        Modulation of the expression of long non-coding RNAs H19, GAS5, and MIAT by endurance exercise in the hearts of rats with myocardial infarction.
        Cardiovasc Toxicol. 2021; 21: 162-168
        • Safaei S.
        • Tahmasebi-Birgani M.
        • Bijanzadeh M.
        • Seyedian S.M.
        Increased expression level of long noncoding RNA H19 in plasma of patients with myocardial infarction.
        Int J Mol Cell Med. 2020; 9: 122-129
        • Han Y.
        • Dong B.
        • Chen M.
        • Yao C.
        LncRNA H19 suppresses pyroptosis of cardiomyocytes to attenuate myocardial infarction in a PBX3/CYP1B1-dependent manner.
        Mol Cell Biochem. 2021; 476: 1387-1400
        • Amado L.C.
        • Saliaris A.P.
        • Schuleri K.H.
        • St John M.
        • Xie J.-S.
        • Cattaneo S.
        • et al.
        Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction.
        Proc Natl Acad Sci USA. 2005; 102: 11474-11479
        • Cai B.
        • Tan X.
        • Zhang Y.
        • Li X.
        • Wang X.
        • Zhu J.
        • et al.
        Mesenchymal stem cells and cardiomyocytes interplay to prevent myocardial hypertrophy.
        Stem Cells Transl Med. 2015; 4: 1425-1435
        • Cai B.
        • Ma W.
        • Bi C.
        • Yang F.
        • Zhang L.
        • Han Z.
        • et al.
        Long non-coding RNA H19 mediates melatonin inhibition of premature senescence of c-kit(+) cardiac progenitor cells by promoting miR-675.
        J Pineal Res. 2016; 61: 82-95
        • Huang P.
        • Wang L.
        • Li Q.
        • Tian X.
        • Xu J.
        • Xu J.
        • et al.
        Atorvastatin enhances the therapeutic efficacy of mesenchymal stem cells derived exosomes in acute myocardial infarction via up-regulating long non-coding RNA H19.
        Cardiovasc Res. 2020; 116: 353-367
        • Benjamin E.J.
        • Blaha M.J.
        • Chiuve S.E.
        • Cushman M.
        • Das S.R.
        • Deo R.
        • et al.
        Heart disease and stroke Statistics-2017 update: a report from the American Heart Association.
        Circulation. 2017; 135: e146-e603
        • Gong L.-C.
        • Xu H.-M.
        • Guo G.-L.
        • Zhang T.
        • Shi J.-W.
        • Chang C.
        Long non-coding RNA H19 protects H9c2 cells against hypoxia-induced injury by targeting MicroRNA-139.
        Cell Physiol Biochem. 2017; 44: 857-869
        • Zhang X.
        • Cheng L.
        • Xu L.
        • Zhang Y.
        • Yang Y.
        • Fu Q.
        • et al.
        The lncRNA, H19 mediates the protective effect of hypoxia postconditioning against hypoxia–reoxygenation injury to senescent cardiomyocytes by targeting microRNA-29b-3p.
        Shock. 2019; 52: 249-256
        • Nazir S.
        • Tachamo N.
        • Lohani S.
        • Hingorani R.
        • Poudel D.R.
        • Donato A.
        Acute myocardial infarction and antiphospholipid antibody syndrome: a systematic review.
        Coron Artery Dis. 2017; 28: 332-335
        • Yu B.-Y.
        • Dong B.
        LncRNA H19 regulates cardiomyocyte apoptosis and acute myocardial infarction by targeting miR-29b.
        Int J Cardiol. 2018; 271: 25
        • Zhang B.-F.
        • Chen J.
        • Jiang H.
        LncRNA H19 ameliorates myocardial ischemia-reperfusion injury by targeting miR-22-3P.
        Int J Cardiol. 2019; 278: 224
        • Wang X.
        • Zou M.
        • Li J.
        • Wang B.
        • Zhang Q.
        • Liu F.
        • et al.
        LncRNA H19 targets miR-22 to modulate H2 O2 - induced deregulation in nucleus pulposus cell senescence, proliferation, and ECM synthesis through Wnt signaling.
        J Cell Biochem. 2018; 119: 4990-5002
        • Members W.G.
        • Mozaffarian D.
        • Benjamin E.J.
        • Go A.S.
        • Arnett D.K.
        • Blaha M.J.
        • et al.
        Executive Summary: Heart Disease and Stroke Statistics–2016 Update: a report from the American Heart Association.
        Circulation. 2016; 133: 447-454
        • Hanson M.A.
        • Fareed M.T.
        • Argenio S.L.
        • Agunwamba A.O.
        • Hanson T.R.
        Coronary artery disease.
        Prim Care. 2013; 40: 1-16
        • Steg P.G.
        • Ducrocq G.
        Future of the prevention and treatment of coronary artery disease.
        Circ J. 2016; 80: 1067-1072
        • Kaikkonen M.U.
        • Lam M.T.Y.
        • Glass C.K.
        Non-coding RNAs as regulators of gene expression and epigenetics.
        Cardiovasc Res. 2011; 90: 430-440
        • Xiong G.
        • Jiang X.
        • Song T.
        The overexpression of lncRNA H19 as a diagnostic marker for coronary artery disease.
        Rev Assoc Med Bras (1992). 2019; 65: 110-117
        • Robbins C.S.
        • Hilgendorf I.
        • Weber G.F.
        • Theurl I.
        • Iwamoto Y.
        • Figueiredo J.-L.
        • et al.
        Local proliferation dominates lesional macrophage accumulation in atherosclerosis.
        Nat Med. 2013; 19: 1166-1172
        • Han D.K.
        • Khaing Z.Z.
        • Pollock R.A.
        • Haudenschild C.C.
        • Liau G.
        H19, a marker of developmental transition, is reexpressed in human atherosclerotic plaques and is regulated by the insulin family of growth factors in cultured rabbit smooth muscle cells.
        J Clin Invest. 1996; 97: 1276-1285
        • Kim D.K.
        • Zhang L.
        • Dzau V.J.
        • Pratt R.E.
        H19, a developmentally regulated gene, is reexpressed in rat vascular smooth muscle cells afer injury.
        J Clin Invest. 1994; 93: 355-360
        • Zhang L.
        • Lou D.
        • He D.
        • Wang Y.
        • Wu Y.
        • Cao X.
        • et al.
        Dysregulated circulating apoptosis- and autophagy-related lncRNAs as diagnostic markers in coronary artery disease.
        BioMed Res Int. 2021; : 2021
        • Cao T.
        • Jiang Y.
        • Li D.
        • Sun X.
        • Zhang Y.
        • Qin L.
        • et al.
        H19/TET1 axis promotes TGF-β signaling linked to endothelial-to-mesenchymal transition.
        FASEB J. 2020; 34: 8625-8640
        • Hughes S.E.
        • McKenna W.J.
        New insights into the pathology of inherited cardiomyopathy.
        Heart. 2005; 91: 257-264
        • Zhang Y.
        • Zhang M.
        • Xu W.
        • Chen J.
        • Zhou X.
        The long non-coding RNA H19 promotes cardiomyocyte apoptosis in dilated cardiomyopathy.
        Oncotarget. 2017; 8: 28588-28594
        • Frey N.
        • Olson E.N.
        Cardiac hypertrophy: the good, the bad, and the ugly.
        Annu Rev Physiol. 2003; 65: 45-79
        • Harvey P.A.
        • Leinwand L.A.
        The cell biology of disease: cellular mechanisms of cardiomyopathy.
        J Cell Biol. 2011; 194: 355-365
        • Lyon R.C.
        • Zanella F.
        • Omens J.H.
        • Sheikh F.
        Mechanotransduction in cardiac hypertrophy and failure.
        Circ Res. 2015; 116: 1462-1476
        • Braunwald E.
        The war against heart failure: the Lancet lecture.
        Lancet. 2015; 385: 812-824
        • Li D.
        • Chen G.
        • Yang J.
        • Fan X.
        • Gong Y.
        • Xu G.
        • et al.
        Transcriptome analysis reveals distinct patterns of long noncoding RNAs in heart and plasma of mice with heart failure.
        PLoS One. 2013; 8: e77938
        • Sun L.
        • Zhang Y.
        • Zhang Y.
        • Gu Y.
        • Xuan L.
        • Liu S.
        • et al.
        Expression profile of long non-coding RNAs in a mouse model of cardiac hypertrophy.
        Int J Cardiol. 2014; 177: 73-75
        • Gómez J.
        • Lorca R.
        • Reguero J.R.
        • Martín M.
        • Morís C.
        • Alonso B.
        • et al.
        Genetic variation at the long noncoding RNA H19 gene is associated with the risk of hypertrophic cardiomyopathy.
        Epigenomics. 2018; 10: 865-873
        • Wenhua S.W.
        • Huo Q.
        • Wu H.
        • Wang L.
        • Ding X.
        • Liang L.
        • et al.
        The function of LncRNA-H19 in cardiac hypertrophy.
        Cell Biosci. 2021; 11: 153
        • Aneja A.
        • Tang W.H.
        • Bansilal S.
        • Garcia M.J.
        • Farkouh M.E.
        Diabetic cardiomyopathy: insights into pathogenesis, diagnostic challenges, and therapeutic options.
        Am J Med. 2008; 121: 748-757
        • Zhuo C.
        • Jiang R.
        • Lin X.
        • Shao M.
        LncRNA H19 inhibits autophagy by epigenetically silencing of DIRAS3 in diabetic cardiomyopathy.
        Oncotarget. 2017; 8: 1429-1437
        • Li X.
        • Wang H.
        • Yao B.
        • Xu W.
        • Chen J.
        • Zhou X.
        lncRNA H19/miR-675 axis regulates cardiomyocyte apoptosis by targeting VDAC1 in diabetic cardiomyopathy.
        Sci Rep. 2016; 6: 36340
        • O’Shea P.
        • Griffin M.D.
        • FitzGibbon M.
        Hypertension: The role of biochemistry in the diagnosis and management.
        Clin Chim Acta. 2017; 465: 131-143
        • Lau E.M.T.
        • Giannoulatou E.
        • Celermajer D.S.
        • Humbert M.
        Epidemiology and treatment of pulmonary arterial hypertension.
        Nat Rev Cardiol. 2017; 14: 603-614
        • Omura J.
        • Habbout K.
        • Shimauchi T.
        • Wu W.-H.
        • Breuils-Bonnet S.
        • Tremblay E.
        • et al.
        Identification of long noncoding RNA H19 as a new biomarker and therapeutic target in right ventricular failure in pulmonary arterial hypertension.
        Circulation. 2020; Oct 13: 1464-1484
        • Wang R.
        • Zhou S.
        • Wu P.
        • Li M.
        • Ding X.
        • Sun L.
        • et al.
        Identifying involvement of H19-miR-675-3p-IGF1R and H19-miR-200a-PDCD4 in treating pulmonary hypertension with melatonin.
        Mol Ther Nucleic Acids. 2018; 13: 44-54
        • Su H.
        • Xu X.
        • Yan C.
        • Shi Y.
        • Hu Y.
        • Dong L.
        • et al.
        LncRNA H19 promotes the proliferation of pulmonary artery smooth muscle cells through AT 1 R via sponging let-7b in monocrotaline-induced pulmonary arterial hypertension.
        Respir Res. 2018; 19: 254
        • Visscher T.L.S.
        • Lakerveld J.
        • Olsen N.
        • Küpers L.
        • Ramalho S.
        • Keaver L.
        • et al.
        Perceived health status: is obesity perceived as a risk factor and disease?.
        Obes Facts. 2017; 10: 52-60
        • Alpert M.A.
        • Omran J.
        • Bostick B.P.
        Effects of obesity on cardiovascular hemodynamics, cardiac morphology, and ventricular function.
        Curr Obes Rep. 2016; 5: 424-434
        • Cavalera M.
        • Wang J.
        • Frangogiannis N.G.
        Obesity, metabolic dysfunction, and cardiac fibrosis: pathophysiological pathways, molecular mechanisms, and therapeutic opportunities.
        Transl Res. 2014; 164: 323-335
        • Liu Y.
        • Xu X.-Y.
        • Shen Y.
        • Ye C.-F.
        • Hu N.
        • Yao Q.
        • et al.
        Ghrelin protects against obesity-induced myocardial injury by regulating the lncRNA H19/miR-29a/IGF-1 signaling axis.
        Exp Mol Pathol. 2020; 114: 104405