Vasoactive mediators in congenital heart diseases with shunt lesions and pulmonary hypertension
Increased pulmonary flow in left-to-right shunt lesions and decreased pulmonary flow and hypoxia in right-to-left shunt lesions constitute the main cause of morbidity and mortality in congenital heart diseases. This study was planned to determine the relation of vasoactive mediators and pulmonary hypertension in congenital heart disease with shunt lesions. Materials and methods: Patients (31 females, 22 males; 5 months to 16 years old) were divided into 2 groups according to their shunt lesions (acyanotic, cyanotic), pulmonary artery mean pressure (below 30 mmHg: nonhypertensive, above 30 mmHg: hypertensive), and pulmonary resistance (below 2 U/m2: low, above 2 U/m2: high). The acyanotic group was further divided into subgroups based on pulmonary artery mean pressure values. Vascular endothelial growth factor, interleukin 6, interleukin 8, fibroblast growth factor, and endothelin levels were determined in systemic arterial, pulmonary artery, and venous blood samples. Results: All vascular endothelial growth factor levels were significantly elevated in the high pulmonary resistance group. Arterial and venous endothelin levels were significantly elevated in the cyanotic group and high pulmonary resistance group. Positive correlations were found between vascular endothelial growth factor and interleukin 6, interleukin 8, and pulmonary artery systolic pressures. Conclusion: Vascular endothelial growth factors play an important role in the development of irreversible pulmonary hypertension; therefore, evaluation of vascular endothelial growth factor levels could guide the management of treatment.
Vasoactive mediators in congenital heart diseases with shunt lesions and pulmonary hypertension
Increased pulmonary flow in left-to-right shunt lesions and decreased pulmonary flow and hypoxia in right-to-left shunt lesions constitute the main cause of morbidity and mortality in congenital heart diseases. This study was planned to determine the relation of vasoactive mediators and pulmonary hypertension in congenital heart disease with shunt lesions. Materials and methods: Patients (31 females, 22 males; 5 months to 16 years old) were divided into 2 groups according to their shunt lesions (acyanotic, cyanotic), pulmonary artery mean pressure (below 30 mmHg: nonhypertensive, above 30 mmHg: hypertensive), and pulmonary resistance (below 2 U/m2: low, above 2 U/m2: high). The acyanotic group was further divided into subgroups based on pulmonary artery mean pressure values. Vascular endothelial growth factor, interleukin 6, interleukin 8, fibroblast growth factor, and endothelin levels were determined in systemic arterial, pulmonary artery, and venous blood samples. Results: All vascular endothelial growth factor levels were significantly elevated in the high pulmonary resistance group. Arterial and venous endothelin levels were significantly elevated in the cyanotic group and high pulmonary resistance group. Positive correlations were found between vascular endothelial growth factor and interleukin 6, interleukin 8, and pulmonary artery systolic pressures. Conclusion: Vascular endothelial growth factors play an important role in the development of irreversible pulmonary hypertension; therefore, evaluation of vascular endothelial growth factor levels could guide the management of treatment.
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- Clark EB. Etiology of congenital cardiovascular malformations: epidemiology and genetics. In: Allen HD, Gutgesell HP, Clark EB, Driscoll DJ, editors. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2001. pp. 64–79.
- Rabinovitch M. Pathophysiology of pulmonary hypertension. In: Allen HD, Gutgesell HP, Clark EB, Driscoll DJ, editors. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2008. pp. 1322–54.
- Rosenzweig EB, Barst RJ. Clinical management of patients with pulmonary hypertension. In: Allen HD, Gutgesell HP, Clark EB, Driscoll DJ, editors. Moss and Adams’ Heart Disease in Infants, Children, and Adolescents. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2008. p. 1355–69.
- Galiè N, Torbicki A, Barst R, Dartevelle P, Haworth S, Higenbottam T, Olschewski H, Peacock A, Pietra G, Rubin LJ et al. Task Force. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J 2004; 25: 2243–
- Himeno W, Akagi T, Furui J, Maeno Y, Ishii M, Kosai K, Murohara T, Kato H. Increased angiogenic growth factor in cyanotic congenital heart disease. Pediatr Cardiol 2003; 24: 127–32.
- Ootaki Y, Yamaguchi M, Yoshimura N, Oka S, Yoshida M, Hasegawa T. Vascular endothelial growth factor in children with congenital heart disease. Ann Thorac Surg 2003; 75: 1523–6.
- Jiaxin H, Sun P, Ruan X, Chao A, Lin Y, Li XY. Mechanism of myocardial micro vessel formation in cyanotic congenital heart disease. Circ J 2005; 69: 1089–93.
- Hamada H, Ebata R, Higashi K, Tateno S, Niwa K, Honda T, Yasukawa K, Terai M. Serum vascular endothelial growth factor in cyanotic congenital heart disease functionally contributes to endothelial cell kinetics in vitro. Int J Cardiol 2007; 120: 66–71.
- Baghdady Y, Hussein Y, Shahata M. Vascular endothelial growth factor in children with cyanotic and acyanotic congenital heart diseases. Arch Med Sci 2010; 6: 221–5.
- Lam CL, Peterson TE, Croatt AJ, Nath KA, Katusic ZS. Functional adaptation and remodeling of pulmonary artery in flow-induced pulmonary hypertension. Am J Physiol 2005; 289: H2334–41.
- Huang HQ, Zhang P, Wang Z, Tang F, Jiang Z. Activation of endothelin-1 receptor signaling pathways is associated with neointima formation, neoangiogenesis and irreversible pulmonary hypertension in patients with congenital heart disease. Circ J 2011; 75: 1463–71.
- El-Melegy NT, Mohammed NA. Angiogenic biomarkers in children with congenital heart disease: possible implications. Italian J Pediatrics 2010; 36: 32–41.
- El-Chami H, Hasoun PM. Immune and inflammatory mechanism in pulmonary arterial hypertension. Prog Cardiovasc Dis 2012; 55: 218–28.
- Robinson ES, Khankin EV, Karumanchi SA, Humpreys BD. Hypertension induced by VEGF signaling pathway inhibition: mechanisms and potential use as a biomarker. Semin Nephrol 2010; 30: 5091–601.
- Tian J, Fratz S, Hou Y, Lu Q, Görlach A, Hess J, Schreiber C, Datar SA, Oishi P, Nechtman J et al. Delineating the angiogenic gene expression profile before pulmonary vascular remodelling in a lamb model of congenital heart disease. Physiol Genomics 2011; 43: 87–98.
- Steiner MK, Syrkina OL, Kolliputi N, Mark EJ, Hales CA, Waxman AB. Interleukin-6 over expression induces pulmonary hypertension. Circ Res 2009; 104: 236–44.
- Golembeski SM, West J, Tada Y, Fagan KA. Interleukin-6 causes mild pulmonary hypertension and augments hypoxiainduced pulmonary hypertension in mice. Chest 2005; 128: 572S–3S.
- Smadja DM, Gaussem P, Mauge L, Lacroix R, Gandrille S, Remones V, Peyrard S, Sabatier F, Bonnet D, Lévy M. Comparison of endothelial biomarkers according to reversibility of pulmonary hypertension secondary to congenital heart disease. Pediatr Cardiol 2010; 31: 657–62.
- Mabuchi N, Tsutamoto T, Wada A, Ohnishi M, Maeda K, Hayashi M, Kinoshita M. Relationship between interleukin-6 production in the lung and pulmonary vascular resistance in patients with congestive heart failure. Chest 2002; 121: 1195– 20
- Mangi MH, Newland AC. Angiogenesis and angiogenic mediators in hematological malignancies. Br J Haematol 2000; 111: 43–51.
- Bacciolini M, Dewald B, Moser B. Human chemokines: an update. Annu Rev Immunol 1997; 15: 675–705.
- Hu DE, Hori Y, Fan TPD. Interleukin-8 stimulates angiogenesis in rats. Inflammation 1993; 17: 135–43.
- Schweigerer L, Fotsis T. Angiogenesis and angiogenesis inhibitors in pediatric disease. Eur J Pediatr 1991; 151: 472–6.
- Yeager ME, Frid M, Stenmark KR. Progenitor cells in pulmonary vascular remodeling. Pulm Circ 2011; 1: 3–6.
- Bousvaros A, Zurakowski D, Fishman SJ, Keough K, Law T, Sun C, Leichtner AM. Serum basic fibroblast growth factor in pediatric Chrohn’s disease. Dig Dis Sci 1997; 42: 378–86.
- Hasdai D, Barak V, Leibovitz E, Herz I, Sclarovsky S, Eldar M, Scheinowitz M. Serum basic fibroblast growth factor levels in patients with ischemic heart disease. Int J Cardiol 1997; 59: 133–
- Starnes SL, Duncan BW, Kneebone JM, Rosenthal GL, Jones TK, Grifka RG, Cecchin F, Owens DJ, Fearneyhough C, Lupinetti FM. Vascular endothelial growth factor and basic fibroblast growth factor in children with cyanotic congenital heart disease. J Thorac Cardiovasc Surg 2000; 119: 534–9.
- Kedzierski RM, Yanagisawa M. Endothelin system: doubleedged sword in health and disease. Annu Rev Pharmacol Toxicol 2001; 41: 851–76.
- El-Melegy NT, Mohamed NA. Angiogenic biomarkers in children with congenital heart disease: possible implications. Italian J Pediatr 2010; 36: 32–41.
- Tsui JCS, Baker DM, Biecker E, Shaw S, Dashwood MR. Potential role of endothelin 1 in ischemia-induced angiogenesis in critical leg ischemia. Br J Surg 2002; 89: 741–7.
- Baliga RS, MacAllister RJ, Hobbs AJ. New perspectives for the treatment of pulmonary hypertension. British J Pharmacol 2011; 163: 125–40.
- Tutar HE, Imamoglu A, Atalay S, Gumus H, Akar N. Plasma endothelin-1 levels in patients with left-to-right shunt with or without pulmonary hypertension. Int J Cardiol 1999; 70: 57–
- Aggarwal S, Gross C, Fireman JR, Black SM. Oxidative stress and development of endothelial dysfunction congenital heart disease with increased pulmonary blood flow: lessons from the neonatal lamb. Trends Cardiovasc Med 2010; 20: 238–46.
- Hirose S, Hosoda Y, Furuya S, Otsuki T, Ikeda E. Expression of vascular endothelial growth factor and its receptors correlates closely with formation of the plexiform lesion in human pulmonary hypertension. Pathol Int 2000; 50: 472–9.
- D’Orleans-Juste P, Labonte J, Bkaily G, Choufani S, Plante M, Honore JC. Function of endothelin (B) receptor in cardiovascular physiology and pathophysiology. Pharmacol Ther 2002; 95: 221–38.
- Saka OS, Tatsumi K. Vascular remodeling in pulmonary arterial hypertension: multiple cancer-like pathways and possible treatment modalities. Int J Cardiol 2011; 147: 4–12.