©М.О. Гончарь СТАН ФУНКЦІОНАЛЬНОЇ АДАПТАЦІЇ СЕРЦЕВО-СУДИННОЇ СИСТЕМИ У ДІТЕЙ ПІСЛЯ ХІРУРГІЧНОЇ КОРЕКЦІЇ ВРОДЖЕНИХ ВАД СЕРЦЯ Харківський національний медичний університет СТАН ФУНКЦІОНАЛЬНОЇ АДАПТАЦІЇ СЕРЦЕВО-СУДИННОЇ СИСТЕМИ У ДІТЕЙ ПІСЛЯ ХІРУРГІЧНОЇ КОРЕКЦІЇ ВРОДЖЕНИХ ВАД СЕРЦЯ. В результаті обстеження 148 школярів у 73,7% пацієнтів, які були прооперовані з приводу вроджених вад серця, у віддалені терміни спостереження виявлено зниження рівня фізичноїпрацездатності за даними велоергометрі!. У 22,1% дітей встановлено добру толерантність до фізичного навантаження, у 4,2%-задовільну, у 70,7%-знижену, низьку-у 3,0% хворих. Незадовільну толерантність до фізичного навантаження мають діти з комбінованими вадами серця, що мали ускладнення до оперативної корекції. СОСТОЯНИЕ ФУНКЦИОНАЛЬНОЙ АДАПТАЦИИ СЕРДЕЧНО-СОСУДИСТОЙ СИСТЕМЫ У ДЕТЕЙ ПОСЛЕ ХИРУРГИЧЕСКОЙ КОРРЕКЦИИ ВРОЖДЕННЫХ ПОРОКОВ СЕРДЦА. В результате обследования 148 пациентов у 73,7% детей, прооперированных по поводу врожденных пороков сердца, в отдаленные сроки наблюдения по данным велоэргометрии выявлено снижение уровня физической работоспособности. У 22,1% детей выявлена хорошая толерантность к физической нагрузке, у 4,2%-удовлетворительная, у 70,7 %-сниженная, низкая-у 3,0% больных. Неудовлетворительную толерантность кфизической нагрузке имеют дети с комбинированными пороками сердца, имевшие осложнения при оперативной коррекции. CONDITION OF CARDIOVASCULAR FUNCTIONAL ADAPTATION IN CHILDREN AFTER SURGICAL TREATMENT OF CONGENITAL HEART DISEASE. 148 patients after surgical treatment of congenital heart disease have been observed. 73,7% children had impaired tolerance to physical exertion during bicycle ergometry, among them 70,7% patients with decreased and 3,0% with low level. 22,1% children have shown good and 4,2%-satisfactory exercise tolerance. Poor tolerance to physical exertion was typical in children with combined congenital heart disease who had complications during surgery. Ключові слова: вроджені вади серця, міокардиальна дисфункція, велоергометрія. Ключевые слова: врожденные пороки сердца, миокардиальная дисфункция, велоэргометрия.

Objective-Reactive oxygen species have been implicated as signaling molecules modulating the activity of redoxsensitive transcription factors such as nuclear factor kappa B (NF-B). Recently, the transcription factor hypoxiainducible factor-1 (HIF-1), known to mediate gene expression by hypoxia, has been found to be also activated by nonhypoxic factors in a redox-sensitive manner. We therefore aimed to elucidate the link between these 2 important redox-sensitive transcription factors. Methods and Results-In pulmonary artery smooth muscle cells, reactive oxygen species generated either by exogenous H 2 O 2 or by a NOX4-containing NADPH oxidase stimulated by thrombin activated or induced NF-B and HIF-1␣. The reactive oxygen species-mediated HIF-1␣ induction occurred on the transcriptional level and was dependent on NF-B.Transfection experiments with wild-type or mutant HIF-1␣ promoter constructs revealed the presence of a yet unidentified NF-B binding element. Gel shift analyses and chromatin immunoprecipitation verified binding of NF-B to this site. Furthermore, reactive oxygen species enhanced expression of plasminogen activator inhibitor-1, which was prevented by dominant-negative IB or mutation of the HIF-1 binding site within the plasminogen activator inhibitor-1 promoter. Conclusion-These findings show for the first time to our knowledge that reactive oxygen species directly link HIF-1␣and NF-B, implicating an important pathophysiological role of this novel pathway in disorders associated with elevated levels of reactive oxygen species. Key Words: hypoxia-inducible factor Ⅲ NADPH oxidase Ⅲ nuclear factor kappa B Ⅲ reactive oxygen species Ⅲ thrombin O xidative stress has been implicated to play an important role in the pathophysiology of many cardiovascular diseases including systemic and pulmonary hypertension and atherosclerosis as well as in tumor progression and vascularization. [1][2][3] Moderate levels of reactive oxygen species (ROS), especially superoxide anions and hydrogen peroxide, have been shown to activate signaling cascades mediating the responses to vasoactive peptides, growth factors, cytokines, hormones, and coagulation factors, as well as to physical and chemical stress. ROS participate in the regulation of vascular proliferation, migration, apoptosis, modification of the extracellular matrix, and procoagulant activity. 4 -9 Moreover, ROS can activate angiogenesis, 10 a process known to be primarily mediated by vascular endothelial growth factor under hypoxia. Under hypoxia, vascular endothelial growth factor expression is induced by the transcription factor hypoxia-inducible factor-1 (HIF-1). 11 Aside from vascular endothelial growth factor, HIF-1 regulates Ͼ100 genes encoding for metabolic enzymes, growth factors, and factors contributing to modulation of extracellular matrix and thrombosis such as plasminogen activator inhibitor-1 (PAI-1). [12][13][14][15] HIF-1 is composed of an inducible ␣-subunit (HIF-1␣) and a constitutive ␤-subunit (also termed ARNT). 12 HIF-1␣ contains an oxygen-de...

The oxygen sensitive ␣-subunit of the hypoxia-inducible factor-1 (HIF-1) is a major trigger of the cellular response to hypoxia. Although the posttranslational regulation of HIF-1␣ by hypoxia is well known, its transcriptional regulation by hypoxia is still under debate. We, therefore, investigated the regulation of HIF-1␣ mRNA in response to hypoxia in pulmonary artery smooth muscle cells. Hypoxia rapidly enhanced HIF-1␣ mRNA levels and HIF-1␣ promoter activity. Furthermore, inhibition of the phosphatidylinositol 3-kinase (PI3K)/AKT but not extracellular signal-regulated kinase 1/2 pathway blocked the hypoxia-dependent induction of HIF-1␣ mRNA and HIF-1␣ promoter activity, suggesting involvement of a PI3K/AKT-regulated transcription factor. Interestingly, hypoxia also induced nuclear factor-B (NFB) nuclear translocation and activity. In line, expression of the NFB subunits p50 and p65 enhanced HIF-1␣ mRNA levels, whereas blocking of NFB by an inhibitor of nuclear factor-B attenuated HIF-1␣ mRNA induction by hypoxia. Reporter gene assays revealed the presence of an NFB site within the HIF-1␣ promoter, and mutation of this site abolished induction by hypoxia. In line, gel shift analysis and chromatin immunoprecipitation confirmed binding of p50 and p65 NFB subunits to the HIF-1␣ promoter under hypoxia. Together, these findings provide a novel mechanism in which hypoxia induces HIF-1␣ mRNA expression via the PI3K/AKT pathway and activation of NFB.

Children who had undergone cardiac surgery in Germany before the implementation of blood-donor screening for hepatitis C had a substantial risk of acquiring the infection. However, after about 20 years, the virus had spontaneously cleared in many patients. The clinical course in those still infected seems more benign than would be expected in people infected as adults.

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NADPH oxidases generate reactive oxygen species (ROS). We studied the role of NOX4 under hypoxia. Hypoxia enhanced NOX4 expression in lung smooth-muscle cells and lung tissue due to HIF-1α binding and activation of the NOX4 promoter. HIF-1α–dependent NOX4 induction restored ROS levels after hypoxia and induced proliferation by hypoxia. The following citations were not referenced in the reference list or the reference/citation is not styled correctly: Kietzmann et al., 1999.

This study shows that PPVI is feasible and it improves the haemodynamics in a selected patient collective. Apart from one coronary compression, the rate of complications at short-term follow-up was low. Percutaneous pulmonary valve implantation can be performed by experienced interventionalists with similar results as originally published. The intervention is technically challenging and longer clinical follow-up is needed.

Increased levels of reactive oxygen species (ROS) contribute to many cardiovascular diseases. In neutrophils, ROS are generated by a NADPH oxidase containing p22phox and NOX2. NADPH oxidases are also major sources of vascular ROS. Whereas an active NOX2-containing enzyme has been described in endothelial cells, the contribution of recently identified NOX homologues to endothelial ROS production and proliferation has been controversial. The authors, therefore, compared the role of NOX2 with NOX4 and NOX1 in endothelial EaHy926 and human microvascular endothelial cells. NOX2 and NOX4 were abundantly expressed, whereas NOX1 expression was less prominent. NOX2, NOX4, and NOX1 were simultaneously present in a single cell in a perinuclear compartment. NOX2 and NOX4 co-localized with the endoplasmic reticulum (ER) marker calreticulin. Additionally, NOX2 co-localized with F-actin at the plasma membrane. NOX2 and NOX4, which interacted with p22phox, as was shown by bimolecular fluorescent complementation, contributed equally to endothelial ROS production and proliferation, whereas NOX1 depletion did not alter ROS levels under basal conditions. These data show that endothelial cells simultaneously express NOX2, NOX4, and NOX1. NOX2 and NOX4, but not NOX1, equally contributed to ROS generation and proliferation under basal conditions, indicating that a complex relation between NOX homologues controls endothelial function.