Elevated Plasma Connective Tissue Growth Factor Levels in Children with Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

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• 作者：Gang Li ; Li Tang ; Peng Jia ; Jian Zhao ; Dong Liu ; Bin Liu
• 关键词：Connective tissue growth factor ; Pulmonary arterial hypertension ; Congenital heart disease ; Biomarker ; Children
• 刊名：Pediatric Cardiology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：37
• 期：4
• 页码：714-721
• 全文大小：512 KB
• 参考文献：1.Abdulla R (1998) The science and practice of pediatric cardiology. Pediatr Cardiol 19:211CrossRef PubMed
  2.Barst RJ, McGoon M, Torbicki A, Torbicki A, Sitbon O, Krowka MJ, Olschewski H, Gaine S (2004) Diagnosis and differential assessment of pulmonary arterial hypertension. J Am Coll Cardiol 43:40S–47S. doi:10.​1016/​j.​jacc.​2004.​02.​032 CrossRef PubMed
  3.Behnes M, Brueckmann M, Lang S, Weiss C, Ahmad-Nejad P, Neumaier M, Borggrefe M, Hoffmann U (2014) Connective tissue growth factor (CTGF/CCN2): diagnostic and prognostic value in acute heart failure. Clin Res Cardiol 103:107–116. doi:10.​1007/​s00392-013-0626-6 CrossRef PubMed
  4.Bienertova-Vasku J, Novak J, Vasku A (2015) MicroRNAs in pulmonary arterial hypertension: pathogenesis, diagnosis and treatment. J Am Soc Hypertens 9:221–234. doi:10.​1016/​j.​jash.​2014.​12.​011 CrossRef PubMed
  5.Blom IE, Goldschmeding R, Leask A (2002) Gene regulation of connective tissue growth factor: new targets for antifibrotic therapy. Matrix Biol 21:473–482CrossRef PubMed
  6.Bradham DM, Igarashi A, Potter RL, Grotendorst GR (1991) Connective tissue growth factor: a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10. J Cell Biol 114:1285–1294CrossRef PubMed
  7.Cicha I, Garlichs CD, Daniel WG, Goppelt-Struebe M (2004) Activated human platelets release connective tissue growth factor. Thromb Haemost 91:755–760PubMed
  8.Duncan MR, Frazier KS, Abramson S, Williams S, Klapper H, Huang X, Grotendorst GR (1999) Connective tissue growth factor mediates transforming growth factor β-induced collagen synthesis: down-regulation by cAMP. FASEB J 13:1774–1786PubMed
  9.Dziadzio M, Usinger W, Leask A, Abraham D, Black CM, Denton C, Stratton R (2005) N-terminal connective tissue growth factor is a marker of the fibrotic phenotype in scleroderma. QJM 98:485–492CrossRef PubMed
  10.Feltes TF, Bacha E, Beekman RH et al (2011) Indications for cardiac catheterization and intervention in pediatric cardiac disease: a scientific statement from the American Heart Association. Circulation 123:2607–2652. doi:10.​1161/​CIR.​0b013e31821b1f10​ CrossRef PubMed
  11.Gatzoulis MA, Alonso-Gonzalez R, Beghetti M (2009) Pulmonary arterial hypertension in paediatric and adult patients with congenital heart disease. Eur Respir Rev 18:154–161. doi:10.​1183/​09059180.​00003309 CrossRef PubMed
  12.Giannakoulas G, Mouratoglou SA, Gatzoulis MA, Karvounis H (2014) Blood biomarkers and their potential role in pulmonary arterial hypertension associated with congenital heart disease. A systematic review. Int J Cardiol 174:618–623. doi:10.​1016/​j.​ijcard.​2014.​04.​156 CrossRef PubMed
  13.Hanley JA, McNeil BJ (1983) A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology 148:839–843CrossRef PubMed
  14.Hishikawa K, Oemar BS, Tanner FC, Nakaki T, Luscher TF, Fujii T (1999) Connective tissue growth factor induces apoptosis in human breast cancer cell line MCF-7. J Biol Chem 274:37461–37466CrossRef PubMed
  15.Huang X, Zou L, Yu X, Chen M, Guo R, Cai H, Yao D, Xu X, Chen Y, Ding C, Cai X, Wang L (2015) Salidroside attenuates chronic hypoxia-induced pulmonary hypertension via adenosine A2a receptor related mitochondria-dependent apoptosis pathway. J Mol Cell Cardiol 82:153–166. doi:10.​1016/​j.​yjmcc.​2015.​03.​005 CrossRef PubMed
  16.Kato M, Fujisawa T, Hashimoto D, Kono M, Enomoto N, Nakamura Y, Inui N, Hamada E, Miyazaki O, Kurashita S, Maekawa M, Suda T (2014) Plasma connective tissue growth factor levels as potential biomarkers of airway obstruction in patients with asthma. Ann Allergy Asthma Immunol 113:295–300. doi:10.​1016/​j.​anai.​2014.​05.​026 CrossRef PubMed
  17.Klaassen I, van Geest RJ, Kuiper EJ, van Noorden CJ, Schlingemann RO (2015) The role of CTGF in diabetic retinopathy. Exp Eye Res 133:37–48. doi:10.​1016/​j.​exer.​2014.​10.​016 CrossRef PubMed
  18.Koitabashi N, Arai M, Kogure S, Niwano K, Watanabe A, Aoki Y, Maeno T, Nishida T, Kubota S, Takigawa M, Kurabayashi M (2007) Increased connective tissue growth factor relative to brain natriuretic peptide as a determinant of myocardial fibrosis. Hypertension 49:1120–1127CrossRef PubMed
  19.Koitabashi N, Arai M, Niwano K, Watanabe A, Endoh M, Suguta M, Yokoyama T, Tada H, Toyama T, Adachi H, Naito S, Oshima S, Nishida T, Kubota S, Takigawa M, Kurabayashi M (2008) Plasma connective tissue growth factor is a novel potential biomarker of cardiac dysfunction in patients with chronic heart failure. Eur J Heart Fail 10:373–379. doi:10.​1016/​j.​ejheart.​2008.​02.​011 CrossRef PubMed
  20.Kono M, Nakamura Y, Suda T, Kato M, Kaida Y, Hashimoto D, Inui N, Hamada E, Miyazaki O, Kurashita S, Fukamachi I, Endo K, Ng PS, Takehara K, Nakamura H, Maekawa M, Chida K (2011) Plasma CCN2 (connective tissue growth factor; CTGF) is a potential biomarker in idiopathic pulmonary fibrosis (IPF). Clin Chim Acta 412:2211–2215. doi:10.​1016/​j.​cca.​2011.​08.​008 CrossRef PubMed
  21.Koshman YE, Patel N, Chu M, Iyengar R, Kim T, Ersahin C, Lewis W, Heroux A, Samarel AM (2013) Regulation of connective tissue growth factor gene expression and fibrosis in human heart failure. J Card Fail 19:283–294. doi:10.​1016/​j.​cardfail.​2013.​01.​013 CrossRef PubMed PubMedCentral
  22.LaFarge CG, Miettinen OS (1970) The estimation of oxygen consumption. Cardiovasc Res 4:23–30CrossRef PubMed
  23.Leask A, Parapuram SK, Shi-Wen X, Abraham DJ (2009) Connective tissue growth factor (CTGF, CCN2) gene regulation: a potent clinical bio-marker of fibroproliferative disease. J Cell Commun Signal 3:89–94. doi:10.​1007/​s12079-009-0037-7 CrossRef PubMed PubMedCentral
  24.Lee YS, Byun J, Kim JA, Lee JS, Kim KL, Suh YL, Kim JM, Jang HS, Lee JY, Shin IS, Suh W, Jeon ES, Kim DK (2005) Monocrotaline-induced pulmonary hypertension correlates with upregulation of connective tissue growth factor expression in the lung. Exp Mol Med 37:27–35CrossRef PubMed
  25.Li G, Hu Y, Jia P, Fu J, Lu CX, Sun YQ, Liu B (2011) Integrin β3 pathway mediated connective tissue growth factor-induced proliferation, migration and extracellular matrix deposition of pulmonary arterial smooth muscle cells. Zhonghua Er Ke Za Zhi 49:895–900PubMed
  26.Liu B, Wang XM, Zhou TF, Hua YM, Liu HM, Wei L, Qiao LN, Wang XQ, Zhao SS, Shi K (2008) Expression of connective tissue growth factor and its down-regulation by simvastatin administration in pulmonary hypertensive rats. Zhonghua Er Ke Za Zhi 46:359–365PubMed
  27.Miyazaki O, Kurashita S, Fukamachi I, Endo K, Ng PS, Takehara K (2010) Subtraction method for determination of N-terminal connective tissue growth factor. Ann Clin Biochem 47:205–211. doi:10.​1258/​acb.​2010.​009182 CrossRef PubMed
  28.Montani D, Chaumais MC, Guignabert C, Gunther S, Girerd B, Jais X, Algalarrondo V, Price LC, Savale L, Sitbon O, Simonneau G, Humbert M (2014) Targeted therapies in pulmonary arterial hypertension. Pharmacol Ther 141:172–191. doi:10.​1016/​j.​pharmthera.​2013.​10.​002 CrossRef PubMed
  29.Nickel N, Kempf T, Tapken H, Tongers J, Laenger F, Lehmann U, Golpon H, Olsson K, Wilkins MR, Gibbs JS, Hoeper MM, Wollert KC (2008) Growth differentiation factor-15 in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 178:534–541. doi:10.​1164/​rccm.​200802-235OC CrossRef PubMed
  30.Ploegstra MJ, Zijlstra WM, Douwes JM, Hillege HL, Berger RM (2015) Prognostic factors in pediatric pulmonary arterial hypertension: a systematic review and meta-analysis. Int J Cardiol 184:198–207. doi:10.​1016/​j.​ijcard.​2015.​01.​038 CrossRef PubMed
  31.Rhodes CJ, Davidson A, Gibbs JS, Wharton J, Wilkins MR (2009) Therapeutic targets in pulmonary arterial hypertension. Pharmacol Ther 121:69–88. doi:10.​1016/​j.​pharmthera.​2008.​10.​002 CrossRef PubMed
  32.Rosenzweig EB, Feinstein JA, Humpl T, Ivy DD (2009) Pulmonary arterial hypertension in children: diagnostic work-up and challenges. Prog Pediatr Cardiol 27:4–11CrossRef PubMed PubMedCentral
  33.Sakai K, Jawaid S, Sasaki T, Bou-Gharios G, Sakai T (2014) Transforming growth factor-β-independent role of connective tissue growth factor in the development of liver fibrosis. Am J Pathol 184:2611–2617. doi:10.​1016/​j.​ajpath.​2014.​06.​009 CrossRef PubMed PubMedCentral
  34.Simonneau G, Galie N, Rubin LJ, Langleben D, Seeger W, Domenighetti G, Gibbs S, Lebrec D, Speich R, Beghetti M, Rich S, Fishman A (2004) Clinical classification of pulmonary hypertension. J Am Coll Cardiol 43:5S–12SCrossRef PubMed
  35.Voelkel NF, Gomez-Arroyo J, Abbate A, Bogaard HJ, Nicolls MR (2012) Pathobiology of pulmonary arterial hypertension and right ventricular failure. Eur Respir J 40:1555–1565. doi:10.​1183/​09031936.​00046612 CrossRef PubMed PubMedCentral
  36.Wang R, Xu YJ, Liu XS, Zeng DX, Xiang M (2011) Knockdown of connective tissue growth factor by plasmid-based short hairpin RNA prevented pulmonary vascular remodeling in cigarette smoke-exposed rats. Arch Biochem Biophys 508:93–100. doi:10.​1016/​j.​abb.​2011.​01.​019 CrossRef PubMed
  37.Wang R, Xu YJ, Liu XS, Zeng DX, Xiang M (2012) CCN2 promotes cigarette smoke-induced proliferation of rat pulmonary artery smooth muscle cells through upregulating cyclin D1 expression. J Cell Biochem 113:349–359. doi:10.​1002/​jcb.​23361 CrossRef PubMed
  38.Zhu R, He L, Xu J, Zhang Y, Hu Y (2012) Changes of TGF-β1 and CTGF in rats with increased blood flow-induced pulmonary artery hypertension. Zhong Nan Da Xue Xue Bao Yi Xue Ban 37:1013–1020. doi:10.​3969/​j.​issn.​1672-7347.​2012.​10.​008 PubMed
  
• 作者单位：Gang Li (1)
  Li Tang (2)
  Peng Jia (1)
  Jian Zhao (1)
  Dong Liu (1)
  Bin Liu (1)
  
  1. Department of Pediatrics, The First Affiliated Hospital of Sichuan Medical University, No. 25 Taiping Street, Luzhou, 646000, Sichuan, China
  2. Medical Research Center, The First Affiliated Hospital of Sichuan Medical University, Luzhou, 646000, Sichuan, China
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Cardiology
  Cardiac Surgery
  Vascular Surgery
  
• 出版者：Springer New York
• ISSN：1432-1971

文摘

We aimed to investigate plasma connective tissue growth factor (CTGF) levels in pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) (PAH–CHD) in children and the relationships of CTGF with hemodynamic parameters. Plasma CTGF levels were calculated in 30 children with CHD, 30 children with PAH–CHD and 25 health volunteers, using the subtraction method. Cardiac catheterization was performed to measure clinical hemodynamic parameters. Plasma CTGF levels were significantly higher in PAH–CHD than in those with CHD and health volunteers (p < 0.01). In cyanotic PAH–CHD, plasma CTGF levels were significantly elevated compared with acyanotic PAH–CHD in the same group (p < 0.05). Plasma CTGF levels showed positive correlation with B-type natriuretic peptide (BNP) in PAH–CHD (r = 0.475, p < 0.01), while oxygen saturation was inversely related to plasma CTGF levels (r = −0.436, p < 0.05). There was no correlation between CTGF and hemodynamic parameters. Even though the addition of CTGF to BNP did not significantly increase area under curve for diagnosis of PAH–CHD compared with BNP alone (p > 0.05), it revealed a moderately better specificity, positive predictive value and positive likelihood ratio than BNP alone. Plasma CTGF levels could be a promising diagnostic biomarker for PAH–CHD in children.