The dramatic cardiovascular mortality of chronic kidney disease patients is attributable in a significant proportion to endothelial dysfunction. Cyanate, a reactive species in equilibrium with urea, is formed in excess in chronic kidney disease. Cyanate is thought to have a causal role in promoting cardiovascular disease, but the underlying mechanisms remain unclear. Immunohistochemical analysis performed in the present study revealed that carbamylated epitopes associate mainly with endothelial cells in human atherosclerotic lesions. Cyanate treatment of human coronary artery endothelial cells reduced expression of endothelial nitric oxide synthase and increased tissue factor and plasminogen activator inhibitor-1 expression. In mice, administration of cyanate -promoting protein carbamylation at levels observed in uremic patients -attenuated arterial vasorelaxation of aortic rings in response to acetylcholine, without affecting sodium nitroprusside-induced relaxation. Total endothelial nitric oxide synthase and nitric oxide production were significantly reduced in aortic tissue of cyanate-treated mice. This coincided with a marked increase of tissue factor and plasminogen activator inhibitor-1 protein levels in aortas of cyanate-treated mice. These data provide evidence that cyanate compromises endothelial functionality in vitro and in vivo and may contribute to the dramatic cardiovascular risk of patients suffering from chronic kidney disease.

Previously we reported modulation of endothelial prostacyclin and interleukin-8 production, cyclooxygenase-2 expression and vasorelaxation by oleoyl- lysophosphatidylcholine (LPC 18:1). In the present study, we examined the impact of this LPC on nitric oxide (NO) bioavailability in vascular endothelial EA.hy926 cells. Basal NO formation in these cells was decreased by LPC 18:1. This was accompanied with a partial disruption of the active endothelial nitric oxide synthase (eNOS)- dimer, leading to eNOS uncoupling and increased formation of reactive oxygen species (ROS). The LPC 18:1-induced ROS formation was attenuated by the superoxide scavenger Tiron, as well as by the pharmacological inhibitors of eNOS, NADPH oxidases, flavin-containing enzymes and superoxide dismutase (SOD). Intracellular ROS-formation was most prominent in mitochondria, less pronounced in cytosol and undetectable in endoplasmic reticulum. Importantly, Tiron completely prevented the LPC 18:1-induced decrease in NO bioavailability in EA.hy926 cells. The importance of the discovered findings for more in vivo like situations was analyzed by organ bath experiments in mouse aortic rings. LPC 18:1 attenuated the acetylcholine-induced, endothelium dependent vasorelaxation and massively decreased NO bioavailability. We conclude that LPC 18:1 induces eNOS uncoupling and unspecific superoxide production. This results in NO scavenging by ROS, a limited endothelial NO bioavailability and impaired vascular function.

The atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease with a genetically determined dysregulation of the alternative complement pathway, which leads to the development of thrombotic microangiopathy. The application of the targeted therapy in Russia has changed the natural course of the disease since 2012: from death of a patient to achieving a long-term remission of the aHUS. The authors report the clinical case of the aHUS associated with a heterozygous mutation in CFH gene c.2850G>T (p.Gln950His) in a 2 years and 2 months old pediatric patient. The difficulty in diagnosing of the aHUS was the lack of specific laboratory criteria confirming the diagnosis as well as the presence of a diarrheal prodrome at the onset. The diagnosis has been made on the basis of the development of microangiopathic hemolytic anemia, thrombocytopenia, acute kidney injury and the exclusion of other forms of thrombotic microangiopathy. The treatment of the patient in accordance with the clinical guidelines for the management of patients with this nosology proved to be effective and led to a stable remission of the aHUS, which also confirmed the correctness of the diagnosis. The described clinical case observation is of interest to pediatrician physicians and nephrologists. The important factors in the management of such patients are the timely diagnosis of the aHUS along with the initiation of complement-inhibiting Eculizumab therapy.

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Цель. Изучить влияния триметазидина на диастолическую дисфункцию левого желудочка у пациентов с сочетанием ишемической болезни сердца (ИБС) и артериальной гипертонии (АГ). Материал и методы. 154 пациента с сочетанием ИБС и АГ разделены на 2 группы лечения. Пациенты основной группы (n=72) получали базовую терапию и триметазидин 35 мг 2 раза в день. Контрольная группа (n=82) получала только базовую терапию. Исходно и через 2 мес оценивали эхокардиографические показатели, в том числе допплеровские показатели трансмитрального потока. Среди больных основной и контрольной группы на основании результатов эхокардиографии выделены подгруппы пациентов по типу нарушения диастолической функции левого желудочка, в которых проводилось сравнение динамики показателей. Результаты. В основной и контрольной группах на основании результатов эхокардиографии выделены подгруппы пациентов с нарушенной релаксацией (n=54), псевдонормализацией (n=48), рестрикцией (n=52). У больных с нарушенной релаксацией на фоне терапии триметазидином произошло значимое увеличение периода раннего наполнения левого желудочка (на 27,6%; р<0,05) и соотношения обеих фаз заполнения левого желудочка (на 37,8%; р<0,001). Другие изучаемые показатели трансмитрального потока в динамике в остальных подгруппах значимо не изменились. Заключение. Триметазидин 70 мг/сут в комплексной терапии диастолической сердечной недостаточности у пациентов с ИБС и АГ в течение 2-х мес привел к достоверному улучшению некоторых показателей трансмитрального кровотока только у больных с I типом диастолической дисфункции (нарушенной релаксацией). Ключевые слова: триметазидин, гипертрофия миокарда, диастолическая сердечная недостаточность, артериальная гипертония, относительная коронарная недостаточность. Рациональная фармакотерапия в кардиологии 2013;9(4):386-389 Effects of trimetazidine on the transmitral blood flow in patients with diastolic heart failure