The present study aims to evaluate specific biomarkers involved in congenital heart disease (CHD), and whether there is a significant differences between the levels of these biomarkers in the cyanotic CHD (CCHD) and acyanotic CHD (ACHD). We prospectively measured tumor necrosis factor (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), vasoendothelial growth factor (VEGF), troponin T, creatin kinase MB (CKMB), and Caspase 3 levels in 120 consecutive children with CHD (60 cyanotic and 60 a cyanotic with age 1:4 years), and 30 healthy control children. Significant elevated levels of inflammatory markers; TNF-α, IL-6 and CRP was detected in CHD, with percentage increase in cyanotic than a cyanotic subjects as compared to the normal one. Apoptotic biomarker; caspase 3 showed also significant increases in CCHD than ACHD. In addition, tissue injury mechanisms included troponin T and CKMB, exhibited significant increase in cyanotic than a cyanotic CHD. The present results demonstrate also, significant enhancement in remodeling process (VEGF), in cyanotic than a cyanotic patients. Thus, it could be concluded that, the children with CCHD were shown to have elevated levels of inflammatory cytokines, caspase 3, troponin T, and CKMB as these biomarkers may implicated in cardiac functional status.
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Kantor PF, Abraham JR, Dipchand AI, Benson LN, Redington AN. The impact of changing medical therapy on transplantation-free survival in pediatric dilated cardiomyopathy. J Am Coll Cardiol. 2010;55:1377–84.
Takaya J, Ikemoto Y, Teraguchi M, Nogi S, Kobayashi Y. Plasma nitric oxide products correlate with cardiac index of congenital heart disease. Pediatr Cardiol. 2000;21:378–81.
Sharma R, Bolger AP, Li W, Davlouros PA, Volk HD, Poole-Wilson PA, Coats AJ, Gatzoulis MA, Anker SD. Elevated circulating levels of inflammatory cytokines and bacterial endotoxin in adults with congenital heart disease. Am J Cardiol. 2003;92(2): 188–93.
Hamada H, Ebata R, Higashi K, Higeru 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. 2012;120:66–71.
Rakusan K, Cicutti N, Kolar F. Cardiac function, microvascular structure, and capillary hematocrit in hearts of polycythemic rats. Am J Physiol Heart Circ Physiol. 2001;281:H2425–31.
Ratnasamy C, Kinnamon DD, Lipshultz SE, Rusconi P. Associations between neurohormonal and inflammatory activation and heart failure in children. Am Heart J. 2008;155:527–33.
Kantor PF, Rusconi P. Biomarkers in pediatric heart failure: their role in diagnosis and evaluating disease progression. Prog Pediatr Cardiol. 2011;31(1):53–7.
Boffa MC, Karmochkine M. Thrombomodulin: an overview and potential implication in vascular disorders. Lupus. 1998;7(Suppl 2):S120–5.
Cadroy Y, Diquelou A, Dupouy D, Bossavy JP, Sakariassen KS, Sie P. The thrombomodulin protein C/protein S anticoagulant pathway modulates the thrombogenic properties of the normal resting and stimulated endothelium. Arterioscler Thromb Vasc Biol. 1997;17(Suppl 2):520–7.
Horigome H, Murakami T, Isobe T, Nagasawa T, Matsui A. Soluble P-selectin and thrombomodulin-protein C-protein S pathway in cyanotic congenital heart disease with secondary erythrocytosis. Int J Cardiol. 2003;116:e74–5.
Kardys I, Knetsch AM, Bleumink GS. C-reactive protein and risk of heart failure. The Rotterdam study. Am Heart J. 2006;152:514–20.
Lequier LL, Nikaidoh H, Leonard SR, Bokovoy JL, White ML, Scannon PJ, Giroir BP. Preoperative and postoperative endotoxemia in children with congenital heart disease. Chest. 2000;117:1706–12.
Niebauer J, Volk HD, Kemp M, Dominguez M, Schumann RR, Rauchhaus M, Poole-Wilson PA, Coats AJS, Anker SD. Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet. 1999;353:1838–42.
Hasper D, Hummel M, Kleber FX, Reindl I, Volk HD. Systemic inflammation in patients with heart failure. Eur Heart J. 1998;19:761–5.
Adimoolam S, Cooke JP. Endothelium-derived nitric oxide: an antiatherogenic molecule. In: Panza JA, Camnon RO, editors. Endothelium, NO, and atherosclerosis. Armonk: Futura Publishing; 1999. p. 257–67.
Fyfe A, Perloff JK, Niwa K, Child JS, Miner PD. Cyanotic congenital heart disease and coronary artery atherogenesis. Am J Cardiol. 2005;96:283–90.
Paniagua OA, Bryant MB, Panza JA. Role of endothelial nitric oxide in shear stress-induced vasodilatation of human microvasculature. Circulation. 2001;103:1752–8.
Bristow MR. Tumor necrosis factor-α and cardiomyopathy. Circulation. 1998;97:1340–1.
Best PJM, Hasdai D, Sangiorgi G, Schwartz R, Holmes DR Jr, Simari RD, Lerman A. Apoptosis: basic concepts and implications in coronary artery disease. Arterioscler Thromb Vasc Biol. 1999;19:14–22.
Yue T, Ohlstein EH, Ruffolo RR. Apoptosis: a potential target for discovering novel therapies for cardiovascular diseases. Biol Sci. 1999;12:474–9.
Perloff JK, Rosove MH, Sietsema KE, Territo MC. Cyanotic congenital heart disease: a multisystem disorder. In: Perloff JK, Child JS, editors. Congenital heart disease in adults. Philadelphia: Saunders WB Company; 1998. p. 199–226.
Arnal JF, Dinh-Xuan AT, Pueyo M. Endothelial derived nitric oxide and vascular physiology and pathology. Cell Mol Life Sci. 2011;55:1078–87.
Adatia I, Barrow SE, Stratton P, Ritter JM, Haworth SG. Abnormalities in the biosynthesis of thromboxane A2 and prostacyclin in children with cyanotic congenital heart disease. Br Heart J. 1993;69:179–82.
Tempe DK, Virmani S. Coagulation abnormalities in patients with cyanotic congenital heart disease. J Cardiothorac Vasc Anesth. 2002;16:752–65.
Omland T, de Lemos JA, Sabatine MS. A sensitive cardiac troponin T assay in stable coronary artery disease. N Engl J Med. 2009;361:2538–47.
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Nassef, Y.E., Hamed, M.A. & Aly, H.F. Inflammatory Cytokines, Apoptotic, Tissue Injury and Remodeling Biomarkers in Children with Congenital Heart Disease. Ind J Clin Biochem 29, 145–149 (2014). https://doi.org/10.1007/s12291-013-0341-0
- Cyanotic heart disease
- Acyanotic heart disease
- Caspase 3