{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T01:12:12Z","timestamp":1774055532850,"version":"3.50.1"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012131","name":"Department of Science and Technology of Liaoning Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012131","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p><jats:bold>Purpose:<\/jats:bold> Metabolic impairment is one key contributor to heart failure (HF) pathogenesis and progression. The major causes of HF, coronary heart disease (CHD), dilated cardiomyopathy (DCM), and valvular heart disease (VHD) remains poorly characterized in patients with HF from the view of metabolic profile. We sought to determine metabolic differences in CHD-, VHD-, and DCM-induced HF patients and identify significantly altered metabolites and their correlations.<\/jats:p><jats:p><jats:bold>Procedure:<\/jats:bold> In this study, a total of 96 HF cases and 97 controls were enrolled. The contents of 23 amino acids and 26 carnitines in fasting plasma were measured by a targeted liquid chromatography and mass spectrometry (LC-MS) approach.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Nine metabolites (Histidine, Arginine, Citrulline, Glutamine, Valine, hydroxyhexadecenyl-carnitine, acylcarnitine C22, hydroxytetradecanoyl-carnitine, and carnitine) were found to be related with the occurrence of HF. Arginine, Glutamine and hydroxytetradecanoyl-carnitine could effectively distinguish CHD and DCM patients, and hydroxytetradecanoyl-carnitine and aspartic acid were able to classify CHD and VHD cohorts.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> This study indicated that circulating amino acids and long-chain acylcarnitine levels were closely associated with progression of heart failure. Monitoring these metabolic alterations by LC-MS may help the differentiation of CHD, VHD, and DCM in the early stage, and provide new diagnostics targets or therapeutic interventions.<\/jats:p>","DOI":"10.3389\/fcvm.2020.622236","type":"journal-article","created":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T14:07:02Z","timestamp":1611151622000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Characteristics of Blood Metabolic Profile in Coronary Heart Disease, Dilated Cardiomyopathy and Valvular Heart Disease Induced Heart Failure"],"prefix":"10.3389","volume":"7","author":[{"given":"Chang","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruihua","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenguo","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujiao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiyuan","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rihong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1161\/CIRCULATIONAHA.119.040551","article-title":"Unlocking the secrets of mitochondria in the cardiovascular system: path to a cure in heart failure-a report from the 2018 national heart, lung, and blood institute workshop","volume":"140","author":"Tian","year":"2019","journal-title":"Circulation."},{"key":"B2","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/s41572-019-0084-1","article-title":"Dilated cardiomyopathy","volume":"5","author":"Schultheiss","year":"2019","journal-title":"Nat Rev Dis Primers."},{"key":"B3","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1038\/s41569-019-0284-0","article-title":"Genetics of dilated cardiomyopathy: practical implications for heart failure management","volume":"17","author":"Rosenbaum","year":"2020","journal-title":"Nat Rev Cardiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1136\/heartjnl-2018-314403","article-title":"Drug-associated valvular heart diseases and serotonin-related pathways: a meta-analysis","volume":"105","author":"Fortier","year":"2019","journal-title":"Heart."},{"key":"B5","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/s41569-018-0007-y","article-title":"Mechanisms of physiological and pathological cardiac hypertrophy","volume":"15","author":"Nakamura","year":"2018","journal-title":"Nat Rev Cardiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1161\/CIRCRESAHA.118.312017","article-title":"Metabolic coordination of physiological and pathological cardiac remodeling","volume":"123","author":"Gibb","year":"2018","journal-title":"Circ Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e003190","DOI":"10.1161\/JAHA.115.003190","article-title":"Metabolomic profiling identifies novel circulating biomarkers of mitochondrial dysfunction differentially elevated in heart failure with preserved versus reduced ejection fraction: evidence for shared metabolic impairments in clinical heart failure","volume":"5","author":"Hunter","year":"2016","journal-title":"J Am Heart Assoc."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1808","DOI":"10.1161\/CIRCRESAHA.116.306923","article-title":"Molecular and cellular mechanisms of cardiovascular disorders in diabetes","volume":"118","author":"Shah","year":"2016","journal-title":"Circ Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.jacc.2015.10.079","article-title":"Prognostic implications of long-chain acylcarnitines in heart failure and reversibility with mechanical circulatory support","volume":"67","author":"Ahmad","year":"2016","journal-title":"J Am Coll Cardiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1056\/NEJMra063052","article-title":"The failing heart\u2013an engine out of fuel","volume":"356","author":"Neubauer","year":"2007","journal-title":"N Engl J Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1161\/CIRCHEARTFAILURE.114.001469","article-title":"Energy metabolic reprogramming in the hypertrophied and early stage failing heart: a multisystems approach","volume":"7","author":"Lai","year":"2014","journal-title":"Circ Heart Fail."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1820","DOI":"10.1161\/circresaha.116.305420","article-title":"Maintaining ancient organelles: mitochondrial biogenesis and maturation","volume":"116","author":"Vega","year":"2015","journal-title":"Circ Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1161\/CIRCRESAHA.113.300376","article-title":"Cardiac metabolism in heart failure: implications beyond ATP production","volume":"113","author":"Doenst","year":"2013","journal-title":"Circ Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41569-018-0044-6","article-title":"Metabolic remodelling in heart failure","volume":"15","author":"Bertero","year":"2018","journal-title":"Nat Rev Cardiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e012086","DOI":"10.1161\/jaha.119.012086","article-title":"Metabolic remodeling in the pressure-loaded right ventricle: shifts in glucose and fatty acid metabolism-a systematic review and meta-analysis","volume":"8","author":"Koop","year":"2019","journal-title":"J Am Heart Assoc."},{"key":"B16","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.ahj.2012.02.005","article-title":"Baseline metabolomic profiles predict cardiovascular events in patients at risk for coronary artery disease","volume":"163","author":"Shah","year":"2012","journal-title":"Am Heart J."},{"key":"B17","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.atherosclerosis.2013.10.036","article-title":"Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization","volume":"232","author":"Bhattacharya","year":"2014","journal-title":"Atherosclerosis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2843","DOI":"10.1038\/s41467-020-16584-z","article-title":"Core functional nodes and sex-specific pathways in human ischaemic and dilated cardiomyopathy","volume":"11","author":"Li","year":"2020","journal-title":"Nat Commun."},{"key":"B19","first-page":"411","article-title":"The natural history of pancreatic pseudocysts documented by computed tomography","volume":"170","author":"Yeo","year":"1990","journal-title":"Surg Gynecol Obstetrics."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1039\/c5fo00176e","article-title":"The effect of curcumin on liver fibrosis in the rat model of microsurgical cholestasis","volume":"6","author":"Barta","year":"2015","journal-title":"Food Funct."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1002\/ejhf.879","article-title":"Epidemiology, pathophysiology and clinical outcomes for heart failure patients with a mid-range ejection fraction","volume":"19","author":"Rastogi","year":"2017","journal-title":"Eur J Heart Fail."},{"key":"B22","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1016\/j.ijcard.2015.09.114","article-title":"Clinical epidemiology of heart failure with preserved ejection fraction (HFpEF) in comparatively young hospitalized patients","volume":"202","author":"Zacharias","year":"2016","journal-title":"Int J Cardiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"705","DOI":"10.21037\/cdt.2018.10.15","article-title":"Improving medical care and prevention in adults with congenital heart disease-reflections on a global problem-part I: development of congenital cardiology, epidemiology, clinical aspects, heart failure, cardiac arrhythmia","volume":"8","author":"Neidenbach","year":"2018","journal-title":"Cardiovasc Diagn Ther."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e004953","DOI":"10.1161\/CIRCHEARTFAILURE.118.004953","article-title":"Increased cardiac uptake of ketone bodies and free fatty acids in human heart failure and hypertrophic left ventricular remodeling","volume":"11","author":"Voros","year":"2018","journal-title":"Circ Heart Fail."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2324","DOI":"10.1002\/stem.1748","article-title":"The antiproliferative activity of kinase inhibitors in chronic myeloid leukemia cells is mediated by FOXO transcription factors","volume":"32","author":"Pellicano","year":"2014","journal-title":"Stem Cells."},{"key":"B26","doi-asserted-by":"publisher","first-page":"CD013090","DOI":"10.1002\/14651858.CD013090.pub2","article-title":"Xiao Chai Hu Tang, a herbal medicine, for chronic hepatitis B","volume":"2019","author":"Kong","year":"2019","journal-title":"Cochrane Database Syst Rev."},{"key":"B27","doi-asserted-by":"publisher","first-page":"165579","DOI":"10.1016\/j.bbadis.2019.165579","article-title":"Re-balancing cellular energy substrate metabolism to mend the failing heart","volume":"2019","author":"Glatz","year":"2019","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B28","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1161\/CIRCGENETICS.109.852814","article-title":"Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events","volume":"3","author":"Shah","year":"2010","journal-title":"Circ Cardiovasc Genet."},{"key":"B29","doi-asserted-by":"publisher","first-page":"747","DOI":"10.5551\/jat.RV17036","article-title":"Application of metabolomics to epidemiological studies of atherosclerosis and cardiovascular disease","volume":"26","author":"Iida","year":"2019","journal-title":"J Atheroscler Thromb."},{"key":"B30","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1038\/nrcardio.2011.138","article-title":"Metabolomics as a tool for cardiac research","volume":"8","author":"Griffin","year":"2011","journal-title":"Nat Rev Cardiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e003190","DOI":"10.1161\/jaha.115.003190","article-title":"Metabolomic profiling identifies novel circulating biomarkers of mitochondrial dysfunction differentially elevated in heart failure with preserved versus reduced ejection fraction: evidence for shared metabolic impairments in clinical heart failure","volume":"5","author":"Hunter","year":"2016","journal-title":"J Am Heart Assoc."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1016\/j.jacc.2015.02.018","article-title":"Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics","volume":"65","author":"Cheng","year":"2015","journal-title":"J Am Coll Cardiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"3492","DOI":"10.3748\/wjg.v21.i12.3492","article-title":"Long-chain acyl-CoA synthetase in fatty acid metabolism involved in liver and other diseases: an update","volume":"21","author":"Yan","year":"2015","journal-title":"World J Gastroenterol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2736","DOI":"10.1194\/jlr.M700378-JLR200","article-title":"Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome","volume":"48","author":"Watkins","year":"2007","journal-title":"J Lipid Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"913S","DOI":"10.3945\/jn.115.219147","article-title":"Intervention trials with the mediterranean diet in cardiovascular prevention: understanding potential mechanisms through metabolomic profiling","volume":"146","author":"Mart\u00ednez-Gonz\u00e1lez","year":"2016","journal-title":"J Nutr."},{"key":"B36","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1007\/BF03261931","article-title":"Carnitine and acylcarnitines: pharmacokinetic, pharmacological and clinical aspects","volume":"51","author":"Reuter","year":"2012","journal-title":"Clin Pharmacokinet."},{"key":"B37","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1097\/GIM.0b013e3181614289","article-title":"Acylcarnitine profile analysis","volume":"10","author":"Rinaldo","year":"2008","journal-title":"Genet Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.jchromb.2012.07.021","article-title":"Quantification of L-arginine, asymmetric dimethylarginine and symmetric dimethylarginine in human plasma: a step improvement in precision by stable isotope dilution mass spectrometry","volume":"904","author":"Martens-Lobenhoffer","year":"2012","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"6148515","DOI":"10.1155\/2018\/6148515","article-title":"Comparison of three sample preparation procedures for the quantification of l-arginine, asymmetric dimethylarginine, and symmetric dimethylarginine in human plasma using HPLC-FLD","volume":"2018","author":"Schou-Pedersen","year":"2018","journal-title":"J Anal Methods Chem."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.1016\/j.jacc.2009.02.036","article-title":"Diminished global arginine bioavailability and increased arginine catabolism as metabolic profile of increased cardiovascular risk","volume":"53","author":"Tang","year":"2009","journal-title":"J Am Coll Cardiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1095\/biolreprod.114.121384","article-title":"Maternal citrulline supplementation prevents prenatal N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced programmed hypertension in rats","volume":"92","author":"Tain","year":"2015","journal-title":"Biol Reprod."},{"key":"B42","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.atherosclerosis.2008.10.040","article-title":"Asymmetric and symmetric dimethylarginines are of similar predictive value for cardiovascular risk in the general population","volume":"205","author":"Kiechl","year":"2009","journal-title":"Atherosclerosis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1038\/333664a0","article-title":"Vascular endothelial cells synthesize nitric oxide from L-arginine","volume":"333","author":"Palmer","year":"1988","journal-title":"Nature."},{"key":"B44","doi-asserted-by":"crossref","first-page":"23790","DOI":"10.1016\/S0021-9258(18)54352-0","article-title":"Constitutive and inducible nitric oxide synthases incorporate molecular oxygen into both nitric oxide and citrulline","volume":"266","author":"Leone","year":"1991","journal-title":"J Biol Chem."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2012","DOI":"10.1161\/01.cir.83.6.2012","article-title":"Oxidized low density lipoproteins inhibit relaxations of porcine coronary arteries role of scavenger receptor and endothelium-derived nitric oxide","volume":"83","author":"Tanner","year":"1991","journal-title":"Circulation."},{"key":"B46","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1111\/j.1476-5381.1992.tb14237.x","article-title":"Oxidative modification of low-density lipoproteins and the inhibition of relaxations mediated by endothelium-derived nitric oxide in rabbit aorta","volume":"105","author":"Plane","year":"1992","journal-title":"Br J Pharmacol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1172\/JCI114718","article-title":"Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery","volume":"86","author":"Simon","year":"1990","journal-title":"J Clin Invest."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1038\/nm1007-1146b","article-title":"'Multipurpose oxidase' in atherogenesis","volume":"13","author":"Rader","year":"2007","journal-title":"Nat Med"},{"key":"B49","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.1093\/eurheartj\/ehv305","article-title":"Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications","volume":"36","author":"Munzel","year":"2015","journal-title":"Eur Heart J."},{"key":"B50","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/362801a0","article-title":"The pathogenesis of atherosclerosis: a perspective for the 1990s","volume":"362","author":"Ross","year":"1993","journal-title":"Nature."},{"key":"B51","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.atherosclerosis.2004.05.015","article-title":"Inhibition of endothelial nitric oxide generation by low-density lipoprotein is partially prevented by L-arginine and L-ascorbate","volume":"176","author":"Ji","year":"2004","journal-title":"Atherosclerosis."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1016\/s0735-1097(02)02306-9","article-title":"Glycoxidized low-density lipoprotein downregulates endothelial nitricoxide synthase in human coronary cells","volume":"40","author":"Napoli","year":"2002","journal-title":"J Am Coll Cardiol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1016\/j.clnu.2017.10.009","article-title":"Citrulline in health and disease","volume":"37","author":"Papadia","year":"2018","journal-title":"Review on human studies. Clin Nutr."},{"key":"B54","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/s00726-005-0235-4","article-title":"Almost all about citrulline in mammals","volume":"29","author":"Curis","year":"2005","journal-title":"Amino Acids."},{"key":"B55","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1373\/clinchem.2011.169573","article-title":"Metabolomics and cardiovascular biomarker discovery","volume":"58","author":"Rhee","year":"2012","journal-title":"Clin Chem."},{"key":"B56","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1038\/hr.2010.113","article-title":"Metabolomic profiling of uremic solutes in CKD patients","volume":"33","author":"Toyohara","year":"2010","journal-title":"Hypertens Res."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1136\/heartjnl-2016-310391","article-title":"Pathophysiology, diagnosis and treatment of tachycardiomyopathy","volume":"103","author":"Martin","year":"2017","journal-title":"Heart."},{"key":"B58","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.cardfail.2019.09.004","article-title":"Metabolic profiling associates with disease severity in nonischemic dilated cardiomyopathy","volume":"26","author":"Verdonschot","year":"2020","journal-title":"J Card Fail."},{"key":"B59","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1016\/j.hrthm.2008.04.015","article-title":"ACC\/AHA\/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: executive summary","volume":"5","author":"Epstein","year":"2008","journal-title":"Heart Rhythm."},{"key":"B60","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1161\/CIRCRESAHA.114.301863","article-title":"Matrix revisited: mechanisms linking energy substrate metabolism to the function of the heart","volume":"114","author":"Carley","year":"2014","journal-title":"Circ Res."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1161\/CIRCULATIONAHA.105.587519","article-title":"Myocardial structure and function differ in systolic and diastolic heart failure","volume":"113","author":"van Heerebeek","year":"2006","journal-title":"Circulation."},{"key":"B62","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.toxlet.2011.02.013","article-title":"Suppression of phorbol-12-myristate-13-acetate-induced tumor cell invasion by piperine via the inhibition of PKCalpha\/ERK1\/2-dependent matrix metalloproteinase-9 expression","volume":"203","author":"Hwang","year":"2011","journal-title":"Toxicol Lett."},{"key":"B63","doi-asserted-by":"publisher","first-page":"3627","DOI":"10.1016\/j.foodchem.2013.06.028","article-title":"Piperine reverses high fat diet-induced hepatic steatosis and insulin resistance in mice","volume":"141","author":"Choi","year":"2013","journal-title":"Food Chem."},{"key":"B64","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.bbrc.2011.06.153","article-title":"Piperidine alkaloids from piper retrofractum Vahl protect against high-fat diet-induced obesity by regulating lipid metabolism and activating AMP-activated protein kinase","volume":"411","author":"Kim","year":"2011","journal-title":"Biochem Biophys Res Commun."},{"key":"B65","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.ebiom.2017.03.021","article-title":"Piperine attenuates pathological cardiac fibrosis via PPAR-gamma\/AKT pathways","volume":"18","author":"Ma","year":"2017","journal-title":"EBioMedicine."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1253\/circj.cj-14-0510","article-title":"Etiology of valvular heart disease-genetic and developmental origins","volume":"78","author":"Lincoln","year":"2014","journal-title":"Circ J."},{"key":"B67","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1093\/eurheartj\/ehu502","article-title":"The year in cardiology 2014: valvular heart disease","volume":"36","author":"Pierard","year":"2015","journal-title":"Eur Heart J."},{"key":"B68","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1093\/eurheartj\/ehq426","article-title":"Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment","volume":"32","author":"Borlaug","year":"2011","journal-title":"Eur Heart J."},{"key":"B69","doi-asserted-by":"publisher","first-page":"612","DOI":"10.5603\/cj.2012.0113","article-title":"Improvement of ventricular function in systolic heart failure patients with oral L-citrulline supplementation","volume":"19","author":"Balderas-Munoz","year":"2012","journal-title":"Cardiol J."},{"key":"B70","first-page":"612","article-title":"Effect of L-arginine or L-citrulline oral supplementation on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction","volume":"17","author":"Orozco-Gutierrez","year":"2010","journal-title":"Cardiol J."},{"key":"B71","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1097\/MCO.0000000000000340","article-title":"Influence of L-citrulline and watermelon supplementation on vascular function and exercise performance","volume":"20","author":"Figueroa","year":"2017","journal-title":"Curr Opin Clin Nutr Metab Care."},{"key":"B72","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1161\/CIRCGENETICS.114.000223","article-title":"Integrated metabolomics and genomics: systems approaches to biomarkers and mechanisms of cardiovascular disease","volume":"8","author":"Shah","year":"2015","journal-title":"Circ Cardiovasc Genet."},{"key":"B73","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.cardfail.2005.10.012","article-title":"LVAD-induced reverse remodeling: basic and clinical implications for myocardial recovery","volume":"12","author":"Burkhoff","year":"2006","journal-title":"J Card Fail."},{"key":"B74","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/nrcardio.2017.139","article-title":"Reverse remodelling and myocardial recovery in heart failure","volume":"15","author":"Kim","year":"2018","journal-title":"Nat Rev Cardiol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1097\/crd.0000000000000068","article-title":"Reverse remodeling in systolic heart failure","volume":"23","author":"Saraon","year":"2015","journal-title":"Cardiol Rev."},{"key":"B76","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.jacc.2010.11.010","article-title":"Clinical, molecular, and genomic changes in response to a left ventricular assist device","volume":"57","author":"Hall","year":"2011","journal-title":"J Am Coll Cardiol."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2020.622236\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T14:07:04Z","timestamp":1611151624000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2020.622236\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,20]]},"references-count":76,"alternative-id":["10.3389\/fcvm.2020.622236"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2020.622236","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,20]]},"article-number":"622236"}}