Eugeny V. Bedyaev

The regeneration of endothelial cells (ECs) lining arteries, veins, and large lymphatic vessels plays an important role in vascular pathology. To understand the mechanisms of atherogenesis, it is important to determine what happens during endothelial regeneration. A comparison of these processes in the above-mentioned vessels reveals both similarities and some significant differences. Regeneration is carried out by moving intact ECs from the edges of the viable endothelial layer towards the centre of the EC damage zone. A sharp decrease in contact inhibition leads to the spreading of the edges of the ECs situated on the damage border. This stimulates the second row of ECs to enter the S-phase, then the G2 phase of cell cycle, and finally mitosis. In all three types of vessels studied, mitotically dividing ECs were found using correlation light and electron microscopy. These ECs have a body protruding into the lumen of the vessel, covered with micro-villi and other outgrowths. The level of EC rounding and protruding is highest in the arteries and least pronounced in the lymphatic vessels. The intercellular contacts of mitotically dividing cells become wider. The EC division leads to an increase in the density of ECs. ECs moving over the damaged area and partially outside the damaged area acquire a fusiform shape. In the process of regeneration of arterial endothelium, the damaged ECs are removed. Then health ECs move to a surface devoid of endothelium, and detach spreading out, flattened platelets from the luminal surface of the vessel. In the veins, ECs grow on the surface of platelets and microthrombi. In lymphatic vessels, ECs detach from the basement membrane slower than in the veins and arteries. There, the migrating ECs grow under fibrin fibres. After some time (usually after 30 days), the EC mosaic returns to normal in all three types of vessels.

The mechanisms responsible for the growth and development of vascular beds in intestinal villi during postnatal ontogenesis remain enigmatic. For instance, according to the current consensus, in the sprouting type of angiogenesis, there is no blood flow in the rising capillary sprout. However, it is known that biomechanical forces resulting from blood flow play a key role in these processes. Here, we present evidence for the existence of the intussusception type of angiogenesis during the postnatal development of micro-vessel patterns in the intestinal villi of rats. This process is based on the high-level flattening of blood capillaries on the flat surfaces of intestinal villi, contacts among the opposite apical plasma membrane of endothelial cells in the area of inter-endothelial contacts, or the formation of bridges composed of blood leucocytes or local microthrombi. We identified factors that, in our opinion, ensure the splitting of the capillary lumen and the formation of two parallel vessels. These phenomena are in agreement with previously described features of intussusception angiogenesis.

Angiogenesis, or the development of blood vessels by growing from already-formed vessels, is observed in embryonic development, physiological cyclical processes such as wound healing, the encapsulation of foreign bodies, tumor growth, and some other situations. In this review, we analyze the cellular mechanisms of angiogenesis, namely, angiogenesis by sprouting, ansiform (by loop formation) angiogenesis, coalescent angiogenesis, and angiogenesis by intussusception (splitting the capillary into two channels). The analysis of data revealed a lot of unanswered questions and contradictions. Here, we propose several new models of angiogenesis explaining these contradictions.