[Nuclear lamins regulate osteogenic differentiation of mesenchymal stem cells].

Nuclear lamins are the major proteins of nuclear envelope and provide the strength of nuclear membrane as well as the interaction of extra-nuclear structures with components of cell nucleus. Recently, it became clear that lamins not only play a structural role in the cell, but could also regulate cell fate, for example lamins could influence cell differentiation via interaction with components of the Notch signaling pathway. Human mutations in LMNA, encoding lamin A/C lead to diseases commonly referred to as laminopathies. Different mutations cause tissue specific phenotypes that affect predominantly a tissue of mesenchymal origin. The nature of this phenomenon, as well as the mechanisms by which lamins regulate cell differentiation remain poorly understood. The aim of this study was to investigate the effect of different mutations of the LMNA on human mesenchymal stem cell (MSC) osteogenic differentiation, and to explore a possible interaction of lamins and Notch signaling pathway. We modified human MSC with mutant LMNA bearing known mutations with tissue specific phenotype associated with different laminopathies. We have shown that mutations associated with different diseases have different effects on the efficiency of MSC osteogenic differentiation and on the expression of specific osteogenic markers SPP1, IBSP and BGLAP. We have also shown that one of the mechanisms involved in the regulation of MSC differentiation may be an interaction of lamins A/C with components of Notch signaling.

[The informative value of oral mucosal biopsy for the diagnosis of systemic amyloidosis].

One hundred and thirteen oral mucosal biopsy specimens were analyzed in patients suspected of having systemic amyloidosis. Histological, immunohistochemical, and genetic studies and polarized light microscopy revealed oral amyloid deposits in 72.6% of cases, including 63.5% with metabolic syndrome and 36.5% with another etiology of chronic heart failure (coronary heart disease, cardiomyopathy). Systemic amyloidosis was found in 13.4% of cases (hereditary transthyretin, AL, and senile forms in 1.8, 10.5, and 1.1% cases, respectively). An anterior abdominal wall skin flap was a valid location to reveal the systemic forms of amyloidosis. Patients with metabolic syndrome and periodontal diseases may have local oral amyloidosis.

[Oral status and oral mucosa blood circulation changes in patients with chronic heart failure].

The objective of this study was to characterize dental status and oral mucosa blood flow in patients with chronic heart failure and amyloid deposits in oral mucosa. Histological and immunohistochemical analysis of 80 oral mucosa biopsies taken from patients aged 32-72 years with chronic heart failure I-IV NYHA functional class was carried out. It detected a systemic amyloidosis in 15.7% of cases; a local amyloid deposition in oral mucosa was found in 58.5% of cases. Amyloid deposition in oral mucosa was associated with severe chronic generalized periodontitis in more than a half of cases. Amyloid deposits in oral mucosa were revealed more often in patients with metabolic syndrome (63.5%). The article describes dental status and oral mucosa blood flow in patients with heart failure.

[Hypertrophic cardiomyopathy. Clinical and morphological comparisons].

The paper comparatively analyzes myocardial morphology in children and adults with hypertrophic cardiomyopathy. All the cases analyzed had its obstructive form and significant asymmetric left ventricular hypertrophy--hypertrophy of the ventricular septum (VS). When stratifying the risk of sudden death from the obstructive form of the disease in adults, the most important characteristics are shown to be less than 45 years of age, stromal enlargement in the right VS closer to the endocardium of the right ventricle; and in some cases this fact must be considered when choosing a management tactic.

[Desmin-related cardiomyopathy].

The observation of 26 years old patient with desminopathy declared itself by hypertrophied cardiomyopathy with its transformation into restrictive phenotype is presented. The features of pathologic course at the patient were a dominance and diversity of cardiac manifestations. Endomyocardiac biopsy allowed suspecting the desminopathy confirmed by genetic analysis. Morphological features of desmin-related cardiomyopathy were irregular desmin conglomerates mainly located under sarcolemma and an indirect histological signs of idiopathic cardiomyopathy as well nuclear polymorphism, perinuclear "nimbus", chaotic located myofibrils.

[Cardiac manifestations of amyloidosis].

Amyloidosis is shown by a group of diseases with a variability of clinical and morphological manifestations determining difficulties in its diagnosis. The cardiovascular system is commonly the site of involvement in different forms of amyloidosis. The variants of cardiac involvement in the pathological process in amyloidosis are outlined depending on various precursor proteins. The specific features of different forms of cardiopathic amyloidosis are described in relation to its type.

[Cellular aspects of hypertrophic cardiomyopathy pathogenesis: the role of cardiomyocyte polyploidy and activation of the proliferating cell nuclear antigen in the myocardium].

Mechanisms of hypertrophy development in hypertrophic obstructive cardiomyopathy (HOCM) have not been enough investigated. In our study, there have been examined patients with severe HOCM at different ages, including children, and patients with essential arterial hypertension (EAH). There was found, that HOCM in children compared to adults was characterized by considerable interventricular septum (IVS) hypertrophy and it was accompanied by the acceleration of cardiomyocyte polyploidy. The average ploidy level of cardiomyocytes in children with HOCM was higher than analogous indices in adults. The average ploidy level of nuclei, the part of PCNA-positive nuclei and polyploidic nuclei of cardiomyocytes in aduls with HOCM were authentically higher than in patients with EAH. Activation of the nuclear antigen in stromal cells was detected only in patients with HOCM. Our findings provide evidence of an important role of cardiomyocyte polyploidy and activation of the proliferating cell nuclear antigen in development of the myocardial hypertrophy in patients with HOCM.

[Phenomena of "micronucleoli" in cardiomyocytes from patients with idiopathic restrictive cardiomyopathy].

Silver staining was used to estimate structural and functional conditions of cardiomyocyte and stromal cell nucleoli in myocardium from 3 patients with idiopathic restrictive cardiomyopathy (RCM). We revealed a prominent increase in the amount of myocardial stromal component cells. The area of nuclei, the area and amount of nucleoli in cells of myocardial stromal component much varied. In some cells of myocardial stromal component we found nuclei, whose area was comparable with that of cardiomyocyte nuclei. In all patients we revealed cardiomyocytes with extranucleolar distribution of argentophilic substance in the nuclei. These data suggest an important pathogenic role of structural rearrangments in the nuclei of cardiomyocytes and stromal component cells in providing specific cell phenotype of myocardium in patients with idiopathic RCM. Extranucleolar (atypical) distribution of argentophilic substance in the nucleus, referred to as "micronucleoli", point out certain disturbances of nucleolar functions in cardiomyocytes in patients with RCM.

[Apoptosis and heart disorders]. / Apoptoz i zabolevaniia serdtsa.

Papers on the significance of cardiomyocyte apoptosis in cardiovascular disorders development are reviewed. Some distinctive features of regulation and morphological manifestations of cardiomyocyte apoptosis are described. Although a great majority of cardiomyocytes are highly differentiated cells, apoptosis-related loss of cellular weight is noted in the number of pathological processes. Data on the role of apoptosis in myocardial ischemia in cardiomyopathies and in heart failure are presented.

[Elevated expression of argentophilic proteins from the nucleolar organizer regions in myocardium of patients with obstructive hypertrophic cardiomyopathy and mutations in p53 tumor suppressor gene]. / Povyshennaia ékspressiia argentofil'nykh belkov oblastei iadryshkovogo organizatora v miokarde bol'nykh obstruktivnoi gipertroficheskoi kardiomiopatiei i mutatsii v gene opukholevogo supressora p53.

Silver staining for nucleolar proteins was used to evaluate the ribosomal genes activity in cardiomyocytes (Cm) and fibroblast-like cells (FBS) of intraventricular septum, and other regions of the left ventricle. Specimens to be analysed were taken from 7 patients with idiopathic obstructive hypertrophic cardiomyopathy (OHCM). In this group the quantity of nucleoli and AgNORs, reflecting the transcriptional and processing level of pre-ribosomal RNA in all type of cells, was at least 2 and 3 times higher than in patients with essential hypertension and in healthy control, respectively. We suggest that nucleolar hypertrophy in patients with hypertrophic cardiomyopathies, inappropriate to hypertrophy in other pathological conditions, may be most probably of compensatory character, and this may be in part explained by nuclear hyperploidy and chromosomal endoreduplication. We have noted a marked heterogeneity in shape, size and quantity of nucleoli, and in AgNORs of FBC. Nuclei with modulated phenotype containing nucleoli of high activity were revealed. This article presents the first data on p53 mutation identification in patients with advanced OHCM.

[Activity of the nucleolar organizers in cardiomyocytes of patients with arterial hypertension of varying genesis]. / Aktivnost' iadryshkovykh organizatorov v kardiomiotsitakh bol'nykh s arterial'noi gipertenziei razlichnogo geneza.

A comparative study of the myocyte nucleolar organizer activity (NOA) was performed on silver-stained myocardium from 6 patients who had died from the hypertension disease and 7 others patients with secondary renal hypertension non-complicated by severe coronary atherosclerosis and heart failure. In the first group, positive correlations between NOA of cardiac cells and the level of maximal diastolic pressure (r = 0.8, p less than 0.028), wall thickness of the left ventricle (r = 0.8, p less than 0.028) as well as myocardial weight (r = 1.0, p less than 0.001) were found. In the second group, on the contrary, there was a pronounced negative correlation between NOA of the myocytes and myocardial weight (r = -0.86, p less than 0.005) which may be explained partially by a primary metabolic myocardial deficiency in such patients.