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In normal conditions vascular system is in equilibrium, the processes of angiogenesis and vascular regression are precisely regulated. The mechanisms underlying the cardiovascular and cancer diseases are the insufficient or excessive angiogenesis, correspondingly. Understanding the mechanisms of angiogenesis is necessary for the development of new approaches to cure these diseases. The fundamental knowledge of the vascular growth and maturation mechanisms formed the basis for the strategy of «therapeutic angiogenesis», which is one of the rapidly developing technologies in regenerative medicine in the world. The strategy is based on the stimulation of blood vessel growth and remodeling in ischemic tissues via administration of recombinant angiogenic factors or genetic constructs for their expression. The same knowledge of the mechanisms of angiogenesis is necessary in the development of new drugs aimed at inhibiting the vascular growth in excessive or aberrant angiogenesis, which escapes the physiological control in various diseases. Herein we review the fundamental molecular and cellular mechanisms of regulation of blood vessel initiation, growth, and stabilization in normal and pathological conditions.

The morphometric study of cytoarchitecture of the structural and functional components of lymph nodes of male monkeys (Macaca mulatta) aged 4-5 years was performed after 8-days-long immersion in water. Activation of lymphocyte mitotic activity in lymphoid nodules (B-dependent zones) was demonstrated in association with an accumulation of small lymphocytes in them and an increase of macrophage reaction. Accumulation of mature forms of plasma cells was detected in all the structures of lymph nodes. It was also found that 8-days-long immersion in water resulted in remodeling of the vessels of lymph node microcirculatory bed, which was accompanied by changes of the endothelium in blood vessel wall and by disturbances of lymph drainage, that lead to accumulation of lymphocytes in lymph node sinuses.

Elevated serum LDL level, which results in cholesterol accumulation in vascular wall, is widely accepted as a risk factor in atherosclerosis development. Additionally to metabolic effects, LDL can produce hormone-like effects in a number of cells: activate second messenger systems, regulate gene expression and activate platelets and stimulate cell proliferation. The responses elicited by LDL are rapid, dose-dependent and capable of being saturated, indicating the involvement of specific receptor/binding sites in LDI-stimulated signal transduction. This LDL-binding protein was isolated from human aorta media and identified as T-cadherin. Cadherins are a superfamily of adhesion molecules that mediate Ca2+ -dependent cell-cell adhesion in embryogenesis and in adult organism's solid tissues. Intercellular junctions are formed as a result of interactions between extracellular domains of the neighboring cells' cadherins. Binding of the intercellular domain to the acting cytoskeleton ensures stability of cadherin-mediated adhesive junctions. T-cadherin is a unique member of calcium-dependent adherent proteins; in contrast to classical cadherins T-cadherin is anchored to the cell surface membranes via a glycosyl phosphatidyl inositol (GPI) moiety. Subcellular distribution of T-cadherin is restricted to lipid rafts on the cell membranes where it co-localizes with signal-transducing molecules. The function of T-cadherin has not yet been revealed. It was originally cloned from chicken embryo brain where the spatial-temporally restricted pattern of T-cadherin suggests its role as a negative guidance cue in tegulating the segmental organization of trunk neural crest migration and motor axon projections. Comparative study of the T-cadherin expression in human organs and tissues revealed that T-cadherin content was maximal in cardiovascular system. Its expression in VSMC depends on the cell phenotype and proliferate activity and increases in atherosclerotic lesion and restenosis. T-cadherin seems to play a key role in the regulation of the vascular cell phenotype, migration and growth. We hypothesize that T-cadherin is an anti-adhesive molecule which participates in intercellular interactions informing cells about their environment and regulating migration and proliferation of cells in vascular wall, while LDL interfere with the normal function of T-cadherin.

Using ultrastructural computer tomography, 3-dimensional models of nucleoli of nucleolonemal, intermediate and circular types as well as of their Ag-NOR-protein distribution were developed for the endotheliocytes of the blood vessels of microcirculatory bed in white rats. It was demonstrated that the maturation process was associated with a decline in fibrillar center numbers, in dense fibrillar component and in other nucleolar subcomponents, while their spatial interrelationships were found to undergo significant changes. Dynamics of reorganization of Ag-NOR-protein distribution in these nucleoli also indicates the substantial reduction of transcription.

The main pathways of regulation of cytoplasm Ca2+ level with hormones and growth factors, as well as mechanisms of regulation of G-proteins, phospholipase C, Ca-channels, adenylate cyclase, guanylate cyclase, and protein kinase C, are discussed. Regulation of cytoplasm Ca2+ in vascular and blood cells with inositol phosphates, cAMP and cGMP, is stressed. The review summarises data on membrane receptors, G-proteins, protein kinases and their targets involved in regulation of Ca2+ turnover in platelets, endothelial and smooth muscle cells.

Urokinase is the main component of the fibrinolytic system and comprises two functions. Namely, the catalytic domain enables to trigger the proteolytic cascade in blood and in the vessel wall, stimulating the activation of growth factors, matrix remodelling and smooth muscle cell proliferation. On the other hand, the amino terminal domain of urokinase that is homologous to epidermal growth factor promotes urokinase to bind to the specific receptor. The cell surface binding of uPA may initiate the activation of the second messengers, protein phosphorylation and cell migration. This dual function of urokinase affects vascular growth, as well as the intimal thickening of the vessel wall after intravascular injury. Also uPA and its receptor are implicated in many physiological and pathological processes, including ovulation, embryogenesis, cancer metastasis, inflammation, and wound healing.

Canalization of the jugular lymphatic sac is accompanied with disengagement from the blood stream of the thoracic subcardinal and the thoracic parts of the superior mesocardinal veins, forming the paired thoracic anlage of the thoracic duct (ThD). Canalization of the retroperitoneal lymphatic sac (RLS) is combined with differentiation of the antevertebral plexus of the abdominal veins, formation of the ThD cistern. Lateroaortal, retrocaval and retroaortal lumbar trunks (LT) become its roots. Together with RLS and the ThD cistern they form the lymphatic "muff" around the abdominal aorta and inferior vena cava. The degree of its parts separation and its substitution by collaterals of LT and by lymph nodes determines the variants of the definitive organization of the ThD initial part. Already at the stage of anlage the intestinal trunk is not included in the ThD root system, but serves as the RLS anterior tributary, or its lumbar, preaortic tributary.

The endothelial lining (EL) of ventricular endocardium and coronary arteries of a dog, minipig and humans, as well as that of the abdominal aorta of a rat and superior vena cava (minipig) was studied using luminescent microscope in the reflected light after staining of the non-fixed tissue with thioflavine-T and argentation. Marked heterogeneity of the endotheliocytes was shown to be both specific and depending on the localization of the cells in the cardiovascular system. Comparative analysis of EL in different animal species and in man, as well as in different parts of the CVS, indicated the relationship between the cellular morphologic features and local hemodynamics.

The article deals with histological properties of the endothelium of the major vessels in mammals and in man. Biological features of this tissue and analysis of its organization are discussed. The material presented justifies consideration of the endothelial lining of the major vessels and veins as a specialized tissue of the vascular system which retains its capacity of capillaroformation. Its epitheliomorphic character and belonging to the angiodermal type of tissues are beyond doubt.

Using scanning electron microscopy, possible ways of the appearance of macrophages on the epithelial surface of the cerebral vascular plexus in rats were studied. The data obtained support the theory which postulates that macrophages are formed in the blood flow or the connective tissue and that subsequently they penetrate through the epithelium of the vascular plexus onto its surface having contact of the cerebrospinal fluid. The structural stages of this process are also reflected in the presented findings.

The article presents a review of present day literature data on the structure of the smooth-muscle cells of vertebrates in the norm and pathology. The smooth-muscle cells of blood vessels and internal organs of vertebrates possess a contractile apparatus the same as in striated muscle and are characterized by two main functions: contractile and synthetical. The latter manifests itself in the capability of the muscle cells to synthesize all the components of the interstitial matter. General pathology of the smooth muscle includes disorders of ultracirculation, metabolic disturbances, necrobiotic changes and necrosis of the muscle cells, compensatory-adaptive processes predominantly of the type of hyperplastic-hypertrophic reaction and regeneration.