Clin Res Cardiol 100, Suppl 1, April 2011

V886 - Cyclooxygenase-2 Expression in Lung in Patients with Congenital Heart Malformations and Pulmonary Arterial Hypertension
T. Loukanov1, C. Sebening1, M. Kirilov2, M. Karck1, M. Gorenflo3
1Klinik für Herzchirurgie, Universitätsklinikum Heidelberg, Heidelberg; 2DKFZ, Heidelberg; 3Abteilung II Schwerpunkt Kinderkardiologie, Universitätskinderklinik Heidelberg, Heidelberg;
Objective: Pulmonary arterial hypertension (PAH) is an important cause of morbidity and mortality in patients with congenital heart disease (CHD) and left-to-right shunt. It has been hypothesised that diverse prostanoides participate in the development of PAH. COX-2, the inducible isoform of COX, is upregulated by hypoxia in pulmonary artery smooth muscle cells, and both elevated thromboxane A2 levels and reduced prostaglandin I2 (PGI2) levels have been demonstrated in patients with idiopathic and secondary forms of PAH. The aim of the present study was to show the potential expression of COX-2 in patients with congenital heart malformations and pulmonary hypertension. We studied expression/localisation of COX isoforms in pulmonary arteries of lung tissue biopsies, and compared the results with the clinical data from the patients.
Patients and methods: Included were all patients with isolated left-to-right shunt undergoing lung biopsy surgery before or concomitantly with intracardiac repair at the Dept. of Cardiac Surgery of the Heidelberg University in the time between 2004 and 2009. All patients with congenital heart defects were investigated with cardiac catheterization. Preoperative pulmonary hypertension was defined as pulmonary artery mean pressure (mean PAP) of more than 25 mmHg. For determination of COX1 and COX2 histological analysis and Immunohistochemistry analysis were done. Additionally a semi quanthative and real-time PCR (polymerase chain reaction) with primers specific for COX-2 and for normalization a HMBS gene (hydroxymethylbilane synthase) expression was used.
Results: Our results showed modest increase in COX1 gene expression and much stronger induction of COX2 after 28 PCR cycles. In order to measure more precisely the induction of those two genes in the patient samples we performed a real time PCR using SYBG chemistry. This experiment confirmed that COX2 is the gene predominantly over expressed in the lung tissue of children with congenital heart disorders (p<0.05).
Conclusions: In this study, we examined the expression of COX2 in pulmonary vascular tissue from human patients with CHD with left-to-right shunt and PAH. We showed that COX2 was constantly expressed in tissues from lung biopsies of the patients. The presented data indicate relationship between COX-2 expression and vascular remodelling in pulmonary arteries in patients with CHD. The potential importance of this finding is to examine further the consequences of COX-2 medical treatment among this patient population.
Clin Res Cardiol 100, Suppl 1, April 2011
Zitierung mit Vortrags- oder Posternummer s.o.
DOI 10.1007/s00392-011-1100-y