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Gudkova A.,Pavlov Medical University | Kostareva A.,Heart Health | Sjoberg G.,Karolinska Institutet | Smolina N.,Heart Health | And 6 more authors.
Pediatric Cardiology | Year: 2013

Desmin cardiomyopathy is a rare cause of congestive heart failure. Its clinical manifestation in adulthood often is associated with conduction disorders and a neuromuscular phenotype. Only a few cases have been reported, with early manifestation in childhood mostly due to severe cardiomyopathy dilationand conduction abnormalities. However, the disease can result in the variety of clinical phenotypes, including hypertrophic, restrictive, and arrthythmogenic cardiomyopathy. This report describes the first case of desmin cardiomyopathy with early manifestation in adolescence and transformation of several clinical phenotypes over time, representing sufficient difficulties for the correct clinical diagnosis and treatment of the disease at an early stage. © 2012 Springer Science+Business Media, LLC.


von Haehling S.,Applied Cachexia Research | von Haehling S.,Center for Cardiovascular Research | Lainscak M.,Applied Cachexia Research | Lainscak M.,University Clinic of Respiratory and Allergic Diseases | And 16 more authors.
Journal of Cachexia, Sarcopenia and Muscle | Year: 2010

Background: Chronic heart failure (CHF) is increasing in prevalence. Patients with CHF usually have co-morbid conditions, but these have been subjected to little research and consequently there is a paucity of guidance on how to manage them. Obesity and diabetes mellitus are common antecedents of CHF and often complicate management and influence outcome. Cachexia is an ominous and often missed sign in patients with CHF. Methods: This manuscript describes the rationale and the design of Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF), a prospective, multicentre, multinational, longitudinal, pathophysiological evaluation study, which is being conducted in 11 centres across six countries in the European Union and in Russia. We aim to recruit >1,600 patients with CHF due to various common aetiologies, irrespective of left ventricular ejection fraction, and with or without co-morbidities at study entry. In addition, >300 patients with type 2 diabetes mellitus without CHF and >150 healthy subjects will serve as control groups. Participants will be systematically investigated at annual intervals for up to 48 months. Additional investigations focusing on cellular and subcellular mechanisms, adipose and skeletal muscle tissue, and in endothelial progenitor cells will be performed in selected subgroups. Conclusions: SICA-HF will provide insights into common co-morbidities in CHF with a specific emphasis on diabetes mellitus and body mass. This will provide a more thorough pathophysiological understanding of the complexity of CHF that will help develop therapies tailored to manage specific co-morbidities. © 2010 The Author(s).


Yaiw K.-C.,Karolinska Institutet | Mohammad A.-A.,Karolinska Institutet | Taher C.,Karolinska Institutet | Wilhelmi V.,Karolinska Institutet | And 14 more authors.
Basic Research in Cardiology | Year: 2014

Both human cytomegalovirus (HCMV) and arginase II (ARG II) have been implicated in the pathogenesis of cardiovascular diseases. The effects of HCMV on ARG II are unknown. The aim of this study was to investigate the effects of HCMV on ARG II expression in endothelial and vascular smooth muscle cells (SMC) both in vitro and ex vivo. Endothelial and SMC were infected with either HCMV or UV-irradiated HCMV. Expression of ARG II, endothelial or inducible nitric oxide synthase (eNOS and iNOS, respectively) and viral immediate early (IE) was quantified using quantitative PCR. Ganciclovir and short interfering RNA were used to determine the viral gene mediating the effects on ARG II. Detection of viral antigens and ARG II expression was performed by immunofluorescence or immunohistochemistry. HCMV infection increased both ARG II mRNA and protein levels in the examined cells; this effect was mediated by the HCMV IE2-p86 protein. The upregulation of ARG II was accompanied by a downregulation of eNOS but an induction of iNOS in HCMV-infected endothelial cells. Both eNOS and iNOS expressions were induced in HCMV-infected SMC. ARG II was abundantly expressed in endothelial cells, foam cells and SMC and was importantly significantly upregulated in HCMV-immunoreactive human carotid atherosclerotic plaques. HCMV IE2-p86 mediates ARG II upregulation in vitro and ARG II is co-expressed with HCMV antigens in human carotid atherosclerotic plaques. We speculate that HCMV may contribute to endothelial dysfunction via ARG II induction and reduced eNOS production. © 2014 Springer-Verlag Berlin Heidelberg.


Sokolova I.B.,RAS Pavlov Institute of Physiology | Fedotova O.R.,Russian Academy of Medical Sciences | Gilerovich E.G.,Russian Academy of Medical Sciences | Sergeev I.V.,RAS Pavlov Institute of Physiology | And 3 more authors.
Advances in Gerontology | Year: 2014

Male Wistar-Kyoto rats (12 and 22-24 months old) were intracerebrally transplanted with syngeneic mesenchymal stem cells (MSCs). Then, the orientation and exploratory behavior of these animals at the age of 2 years (i.e., 1 year or 3 weeks after MSC transplantation) was assessed in an "open field" test. The basic behavioral acts of the older rats (22-24 months old) were inhibited compared to the younger animals (2-3 months old). The transplantation of MSCs did not improve the orientation and exploratory behavior of old rats. The results of morphological and immunohistochemical analysis suggest that the intracerebral MSC transplantation led to partial injury of the ipsilateral hemisphere cortex. © 2014 Pleiades Publishing, Ltd.


Gurova M.M.,Belgorod National Research University | Romanova T.A.,Belgorod National Research University | Novikova V.P.,Almazov Federal Center for Heart | Avilova I.A.,Kursk State University
Biomedical Engineering | Year: 2015

Using gas chromatography–mass spectrometer for studying and evaluating the intestinal microflora in humans with chronic gastroduodenitis compared to traditional methods of diagnosis and microbiological analysis can significantly extend the range of the defined microbiota and its possible changes at different phases of the disease, thus enabling successful correction of microflora and suggesting prospective targeted treatment, followed by evaluation of its effectiveness. The composition and quantity of microorganisms in the intestinal wall of 340 patients aged 12 to 18 years were analyzed using gas chromatography–mass spectrometer in the acute phase, in remission, and at the end of treatment. © 2015 Springer Science+Business Media New York


Zemelko V.I.,Russian Academy of Sciences | Kozhukharova I.B.,Russian Academy of Sciences | Alekseenko L.L.,Russian Academy of Sciences | Domnina A.P.,Russian Academy of Sciences | And 6 more authors.
Cell and Tissue Biology | Year: 2013

Mesenchymal stem cells (MSCs) can be isolated from many adult tissue sources. These cells are a valuable substrate in cell therapy for a substantial number of diseases and injuries. Different types of MSCs vary in plasticity. We performed a comparative study of the neurogenic potential of three types of human MSCs derived from bone marrow (BMSCs), subcutaneous adipose tissue (ADSCs) and endometrium (isolated from the menstrual blood) (eMSCs). It was shown that all three types of MSC cultures demonstrate multipotent plasticity and predisposition to neurogenesis, based on the expression of pluripotency marker SSEA-4 and neuronal precursors markers nestin and beta-III-tubulin. Further analysis revealed a transcription of the neuronal marker MAP2 and neurotrophin-3 in the undifferentiated BMSCs and ADSCs. Additionally, a significant basal level of synthesis of brain-derived neurotrophic factor (BDNF) in the eMSC culture was also observed. Stimulation of neural induction with agents such as 5-azacytidine, recombinant human basic fibroblast growth factor (bFGF), recombinant human epidermal growth factor (EGF), a recombinant human fibroblast growth factor 8 (FGF8), morphogen SHH (sonic hedgehog), retinoic acid (RA) and isobutyl-methyl-xanthine (IBMX), showed further differences in the neurogenic potential of the MSCs. The components of the extracellular matrix, such as Matrigel and laminin, were also the important inducers of differentiation. The most effective neural induction in the BMSCs proceeded without the RA participation while pretreated with 5-azacytidine. In contrary, in case of eMSCs RA was a necessary agent of neural differentiation as it stimulated the transcription of neurotrophin-4 and the elevation of secretion level of BDNF. The use of laminin as the substrate in the derived eMSCs appeared to be critical, though an incubation of the cells with 5-azacytidine was optional. As far as the derived ADSCs, RA in combination with 5-azacytidine caused the elevation of expression of MAP2, but reduced the secretion of BDNF. Thus, the effect of RA on neural differentiation of ADSCs is ambiguous and, together with the study of its signaling pathways in the MSCs, requires further research. The therapeutic effect of transplanted MSCs is commonly explained by their paracrine activity. The high basal level of BDNF synthesis in the eMSCs, along with their high proliferative rate, non-invasive extraction and neural predisposition, is a powerful argument for the use of the intact eMSCs as a substrate in cell therapy to repair a nerve tissue. © 2013 Pleiades Publishing, Ltd.


Dmitrieva R.I.,Almazov Federal Center for Heart | Anisimov S.V.,Russian Academy of Sciences
Cell and Tissue Biology | Year: 2013

Hematopoietic stem cells (HSCs) effectively and continuously replenish the full range of blood-cell populations. Bone-marrow and umbilical-cord blood stem-cell transplantation (SCT) restore hematopoiesis when used in various hematological and oncohematological disorders in adults and children. However, wider clinical application of effective SCT-based approaches is limited by the low number of primitive HSCs in the available biospecimens. Development of effective protocols of HSC expansion in vitro is therefore necessary. In this review, the notion of bone marrow hematopoiesis is discussed as a complex cellular system and a comparative analysis of various methods for HSC expansion in vitro is provided. The review is illustrated by our own data supporting application of various feeder-cell types for human HSC expansion in vitro. © 2013 Pleiades Publishing, Ltd.


Huo Y.,Lund University | Huo Y.,TU Dresden | Mitrofanova L.,Almazov Federal Center for Heart | Orshanskaya V.,Almazov Federal Center for Heart | And 3 more authors.
Journal of Electrocardiology | Year: 2014

Background Fibro-fatty transformation is believed to be the leading cause of deteriorated atrial conduction; however, any direct assessment in relation to P-wave characteristics is lacking. We sought to assess P-wave morphology (PWM) and duration (PWD) in relation to histology of the atrial myocardium. Objective Atrial specimens were collected from 11 patients who died from cardiovascular causes (7 men; median age 73 years). Methods Tissue samples were taken at the level of superior and inferior PVs, center of posterior left atrial wall, terminal crest (CT) and Bachmann's bundle (BB) for assessment of fibro-fatty tissue extent. Standard 12-lead ECGs in sinus rhythm recorded during hospital stay were used for manual assessment of P-wave. Partial interatrial block (pIAB) was defined as a prolonged (≥ 120 ms) and bimodal P-wave in any lead on 12-lead ECG. Results The median PWD was 160 (120-200) ms. Fibrosis extent in CT highly correlated to PWD (r = 0.914, p < 0.001). The combination of fibrosis extent and fatty tissue in BB (16%, range 1%-41%), CT (18%, range 3%-47%) or superior PV (15%, range 6%-24%) correlated to PWD (r = 0.627, p = 0.039; r = 0.795, p = 0.003; and r = 0.668, p = 0.025, respectively). pIAB pattern was observed in 10 subjects; however, it was not associated with either fibrosis or fatty tissue content at any sampling location. Conclusions Our findings further support causal association between PWD and the extent of structural abnormalities in the atrial myocardium and the major atrial conduction routes. © 2014 Elsevier Inc. All rights reserved.


Shlyakhto E.V.,Almazov Federal Center for heart
Vestnik Rossiiskoi Akademii Meditsinskikh Nauk | Year: 2012

This article deals with peculiarities of development and clinical course of heart failure (HF) in diabetic patients, influence of diabetic cardiopathy on HF formation., role of genetic predictors of diabetes mellitus (DM) and HF formation, also the importance of treatment response predictors, the significance of a more personalized exposure in order to optimize treatment. The role of stationary and dynamic genomics was analyzed, especially molecular visualization that allows the earliest possible intervention. The article also includes examples of molecular visualization use in diagnosis of myocardial dysfunction, disease monitoring, and treatment efficacy assessment. Authors give an analysis of targeted treatment methods on the example of targeted delivery of medications to the target-organ (myocard). Discuss means of anti-ischemic myocardial protection, perspectives of metformin use in order to enhance efficacy of myocardial ischemic pre- and postconditioning mechanisms. Presented perspectives of stu^ of molecular and genetic mechanisms involved in the pathogenesis of HF in diabetic patients, in particular, study of key biological feahtres of stem cells, cell interactions, stem cell plasticity (in vitro direction of differentiation) and their paracrine fidnction evaluation. Given information about identification of genes with partly altered expression due to chronic exposure of mesenchymal stem cells to the high concentration of glucose, and upon decreased ability of mesenchymal stem cells ofproangiogenic factors with simultaneous increase of inflammatory markers production (IL8). In whole this article reviews modem state of HF in diabetic patients development mechanisms study with the use of molecular and genetic technologies, and ofperspectives of development of this area.


PubMed | Almazov Federal Center for Heart
Type: Case Reports | Journal: Pediatric cardiology | Year: 2013

Desmin cardiomyopathy is a rare cause of congestive heart failure. Its clinical manifestation in adulthood often is associated with conduction disorders and a neuromuscular phenotype. Only a few cases have been reported, with early manifestation in childhood mostly due to severe cardiomyopathy dilation and conduction abnormalities. However, the disease can result in the variety of clinical phenotypes, including hypertrophic, restrictive, and arrhythmogenic cardiomyopathy. This report describes the first case of desmin cardiomyopathy with early manifestation in adolescence and transformation of several clinical phenotypes over time, representing sufficient difficulties for the correct clinical diagnosis and treatment of the disease at an early stage.

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