ISSN 2149-2263 | E-ISSN 2149-2271
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Circulating matrix metalloproteinases and tissue inhibitors of metalloproteinases levels in pediatric patients with congenital heart disease: Relationship to cardiac functions [Anatol J Cardiol]
Anatol J Cardiol. 2014; 14(6): 531-541 | DOI: 10.5152/akd.2014.4950

Circulating matrix metalloproteinases and tissue inhibitors of metalloproteinases levels in pediatric patients with congenital heart disease: Relationship to cardiac functions

Zübeyir Kılıç1, Birsen Uçar1, Gökmen Özdemir1, Ömer Çolak2, Cengiz Bal3, Türkan Ertuğrul4
1Department of Pediatric Cardiology, Faculty of Medicine, Eskişehir Osmangazi University; Eskisehir-Turkey
2Department of Biochemistry, Faculty of Medicine, Eskişehir Osmangazi University; Eskisehir-Turkey
3Department of Biostatistics, Faculty of Medicine, Eskişehir Osmangazi University; Eskisehir-Turkey
4Department of Pediatric Cardiology, Faculty of Medicine, İstanbul University; İstanbul-Turkey

Objective: The pathological effects of matrix metalloproteinases and their tissue inhibitors in cardiovascular diseases are of considerable interest. In our study, we aimed to determine and evaluate the potential significance of circulating matrix metalloproteinases-2 and 9, tissue inhibitors of matrix metalloproteinases-1 and 2 levels in four patient subgroup of pediatric cardiology field and expose pathophysiologic differences between these groups. Methods: Eighty-seven patients with the diagnosis of congenital heart disease and 47 healthy controls were enrolled in the study. The study group was stratified to 4 subgroups; 14 patients with right ventricular volume overload, 30 patients with left ventricular volume overload, 19 patients with left to right shunt who developed pulmonary hypertension and 24 patients with cyanotic congenital heart disease. For evaluation of the relationships between serum matrix metalloproteinases and their tissue inhibitors levels with cardiac structures and functions; complete blood count, arterial oxygen saturation, detailed echocardiographic measurements (including tissue Doppler) in all patients and hemodynamic parameters of the patients who went to cardiac catheterization were recorded. Serum matrix metalloproteinase levels were determined by ELISA test. Statistical evaluations were performed with SPSS 16.0. For parameters showing normal distribution, comparisons were made with t-test and ANOVA test. However, for parameters without normal distribution, groups were compared with Mann-Whitney U test and Kruskal-Wallis test. Results: We demonstrated that serum tissue inhibitors of matrix metalloproteinases-1 levels of patients with pulmonary hypertension secondary to congenital heart diseases were significantly higher than the patients with left to right shunt without pulmonary hypertension and controls (p<0.01). Although serum matrix metalloproteinases and their tissue inhibitors levels in patients with cyanotic congenital heart diseases and patients with right or left ventricular volume overload were found to be altered when compared with controls but not significant. Conclusion: Our data may suggest the possible role of matrix metalloproteinases and their tissue inhibitors on myocardial remodeling in congenital heart defects and especially in patients who developed pulmonary hypertension.

Keywords: matrix metalloproteinases, tissue inhibitors of metalloproteinases, congenital heart diseases, pulmonary hypertension

Konjenital kalp hastalıklı çocuklarda serum matriks metalloproteinaz ve metalloproteinaz doku inhibitörleri düzeyleri ve kardiyak fonksiyonlarla ilişkisi

Zübeyir Kılıç1, Birsen Uçar1, Gökmen Özdemir1, Ömer Çolak2, Cengiz Bal3, Türkan Ertuğrul4
1Department of Pediatric Cardiology, Faculty of Medicine, Eskişehir Osmangazi University; Eskisehir-Turkey
2Department of Biochemistry, Faculty of Medicine, Eskişehir Osmangazi University; Eskisehir-Turkey
3Department of Biostatistics, Faculty of Medicine, Eskişehir Osmangazi University; Eskisehir-Turkey
4Department of Pediatric Cardiology, Faculty of Medicine, İstanbul University; İstanbul-Turkey

Amaç: Kardiyovasküler hastalıkların gelişiminde, matrix metalloproteinazlar ve bunların spesifik doku inhibitörlerinin etkileri üzerinde durulmaktadır. Çalışmamızın amacı, dört alt grupta incelenen konjenital kalp hastalıklı olgularda matrix metalloproteinaz-2 ve 9, matrix metalloproteinaz doku inhibitörü-1 ve 2 düzeylerini saptayarak; bu gruplardaki patofizyolojik süreç ile ilişkisini göstermekti. Yöntemler: Seksen yedi konjenital kalp hastalıklı ve 47 sağlıklı kontrol çalışmaya alındı. Konjenital kalp hastalığı olan olgular 4 alt gruba ayrıldı: 14 hastada sağ ventrikül volüm yüklenmesi, 30 hastada sol ventrikül volüm yüklenmesi, 19 hastada soldan sağa şanta bağlı gelişen pulmoner hipertansiyon ve 24 hastada siyanotik konjenital kalp hastalığı mevcuttu. Matrix metalloproteinazlar ve bunların doku inhibitörlerinin kardiyak yapı ve fonksiyonlarla ilişkisini değerlendirmek için tüm hastaların tam kan sayımı değerleri, arteriyel oksijen satürasyonu, doku Doppler dahil detaylı ekokardiyografik incelemesi ve kalp kateterizasyonu yapılan hastaların hemodinamik verileri kaydedildi. Matrix metalloproteinazların ve doku inhibitörlerinin düzeyleri, serumda ELISA yöntemiyle çalışıldı. İstatistiksel değerlendirme için SPSS 16.0 programı kullanılırken; normal dağılım gösteren parametreler t-testi ve ANOVA testi, normal dağılım göstermeyen parametreler ise Mann-Whitney U testi ve Kruskal-Wallis testi ile karşılaştırıldı. Bulgular: Soldan-sağa şanta sekonder gelişen pulmoner hipertansiyonlu hastalarda, pulmoner hipertansiyon gelişmemiş hastalar ve kontrollere göre matrix metalloproteinaz-1 doku inhibitörü seviyeleri belirgin yüksek saptandı (p<0,01). Siyanotik konjenital kalp hastalıklı ve sol veya sağ ventrikül volüm yüklenmesi olan olgularda da matrix metalloproteinazlar ve doku inhibitörleri düzeylerinde kontrollere göre bazı farklılıklar gözlenmekle birlikte istatistiksel olarak anlamlı değildi. Sonuç: Bulgularımız, konjenital kalp hastalığı olan, özellikle pulmoner hipertansiyonun geliştiği soldan sağa şantlı çocuklarda matrix metalloproteinazların ve doku inhibitörlerinin kardiyak dokunun yeniden şekillenmesindeki muhtemel rolünü desteklemektedir.

Anahtar Kelimeler: matrix metalloproteinazlar, metalloproteinaz doku inhibitörleri, konjenital kalp hastalığı, pulmoner hipertansiyon

Zübeyir Kılıç, Birsen Uçar, Gökmen Özdemir, Ömer Çolak, Cengiz Bal, Türkan Ertuğrul. Circulating matrix metalloproteinases and tissue inhibitors of metalloproteinases levels in pediatric patients with congenital heart disease: Relationship to cardiac functions. Anatol J Cardiol. 2014; 14(6): 531-541
Manuscript Language: English


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